1
00:00:06,240 --> 00:00:10,320
>>WELCOME I'M CATHERINE LAW

2
00:00:10,320 --> 00:00:23,600
AT NCCIH, NIH

3
00:00:23,600 --> 00:00:33,840
WELCOME TO DAY 1

4
00:00:33,840 --> 00:00:47,200
I WILL TURN OVER TO CO CHAIRS

5
00:00:47,200 --> 00:00:50,280
 TO ALLOW THEM TO WELCOME

6
00:00:50,280 --> 00:00:56,240
 YOU AND FOR THE EVENT.

7
00:00:56,240 --> 00:00:59,960
I AM FROM NIH

8
00:00:59,960 --> 00:01:03,240
 AND I WOULD LIKE TO THANK YOU

9
00:01:03,240 --> 00:01:05,400
 ALL, THE NIH AND U.S. DA STAFF

10
00:01:05,400 --> 00:01:09,160
 AND ALL OF THE SPEAKERS WHO

11
00:01:09,160 --> 00:01:13,760
 HAVE GIVEN OF THEIR TIMES AND

12
00:01:13,760 --> 00:01:16,000
 EXPERTISE TO HELP US AND TO

13
00:01:16,000 --> 00:01:18,920
 ALL OF YOU FOR SHOWING YOUR

14
00:01:18,920 --> 00:01:19,440
 INTEREST.

15
00:01:19,440 --> 00:01:21,080
 WE WANT TO BEGIN THIS MORNING

16
00:01:21,080 --> 00:01:23,240
 WITH A FEW DEFINITIONS TO GET

17
00:01:23,240 --> 00:01:35,920
 EVERYONE ON THE SAME PAGE.

18
00:01:35,920 --> 00:01:41,080
 SO WE LOOK AT THE PROBLEM AND

19
00:01:41,080 --> 00:01:47,720
 MANY INCONSISTENT OUTCOMES

20
00:01:47,720 --> 00:01:50,400
 FROM PROBIOTIC INTERVENTIONS.

21
00:01:50,400 --> 00:01:56,840
 AS YOU KNOW --

22
00:01:56,840 --> 00:01:59,680
 [INDISCERNIBLE]

23
00:01:59,680 --> 00:02:01,760
 SO THEREFORE WE MUST BRIDGE

24
00:02:01,760 --> 00:02:05,640
 THIS GAP AND ALLOW PROBIOTIC

25
00:02:05,640 --> 00:02:10,360
 STRAINS WITH INDIVIDUAL 

26
00:02:10,360 --> 00:02:14,160
 FACTORS INCLUDING MICROBIOME

27
00:02:14,160 --> 00:02:17,920
 AND ENVIRONMENT AND LIFESTYLE.

28
00:02:17,920 --> 00:02:21,160
 WE WILL HAVE QUESTIONS TO

29
00:02:21,160 --> 00:02:24,320
 SERVE AS FUTURE QUESTIONS FOR

30
00:02:24,320 --> 00:02:25,800
 RESEARCH SO I WILL STOP THERE

31
00:02:25,800 --> 00:02:32,360
 AND TURN IT OVER TO MY 

32
00:02:32,360 --> 00:02:33,360
 COADVISOR, Dr. SORKIN.

33
00:02:33,360 --> 00:02:34,560
 >> GOOD MORNING, THANK YOU,

34
00:02:34,560 --> 00:02:34,920
 Dr. KIM.

35
00:02:34,920 --> 00:02:39,320
 I WOULD LIKE TO ADD MY THANKS

36
00:02:39,320 --> 00:02:40,960
 WITH DOCTOR KIM FOR ALL OF YOU

37
00:02:40,960 --> 00:02:41,920
 WHO HELPED PREPARE THIS

38
00:02:41,920 --> 00:02:43,960
 WORKSHOP AND ALL OF YOU

39
00:02:43,960 --> 00:02:44,800
 SHOWING YOUR INTEREST FOR

40
00:02:44,800 --> 00:02:46,400
 JOINING US FOR IT.

41
00:02:46,400 --> 00:02:48,360
 WHILE WE'RE DOING DEFINITIONS,

42
00:02:48,360 --> 00:02:54,160
 LET ME REVIEW THE DEFINITION

43
00:02:54,160 --> 00:02:54,400
 OF DIETARY SUPPLEMENTS.

44
00:02:54,400 --> 00:03:01,800
 THIS IS A DEFINITION OF 

45
00:03:01,800 --> 00:03:03,320
 DIETARY SUPPLEMENTS DEVELOPED

46
00:03:03,320 --> 00:03:06,240
 IN 1994 AND IF YOU LOOK AT IT,

47
00:03:06,240 --> 00:03:07,960
 PROBIOTICS FIT INTO THE

48
00:03:07,960 --> 00:03:10,760
 CATEGORY OF OTHER DIETARY

49
00:03:10,760 --> 00:03:11,160
 SUPPLEMENTS.

50
00:03:11,160 --> 00:03:15,120
 THIS IS WHY THE OFFICE OF

51
00:03:15,120 --> 00:03:16,920
 DIETARY SUPPLEMENTS IS

52
00:03:16,920 --> 00:03:18,960
 INTERESTED IN THIS WORKSHOP

53
00:03:18,960 --> 00:03:21,120
 AND SHARE THE HOPE THAT BY THE

54
00:03:21,120 --> 00:03:23,200
 TIME WE FINISH THE WORKSHOP

55
00:03:23,200 --> 00:03:25,920
 TOMORROW WE WILL HAVE A BETTER

56
00:03:25,920 --> 00:03:27,840
 IDEA OF DEFINING

57
00:03:27,840 --> 00:03:32,040
 INTERVENTIONS, MEASUREMENTS TO

58
00:03:32,040 --> 00:03:33,520
 INCREASE THE EFFICACY OF

59
00:03:33,520 --> 00:03:34,320
 PROBIOTIC INTERVENTIONS, THE

60
00:03:34,320 --> 00:03:36,160
 RESEARCH AND REACH THE FULL

61
00:03:36,160 --> 00:03:38,240
 POTENTIAL OF THIS RESEARCH

62
00:03:38,240 --> 00:03:41,960
 AREA TO ACHIEVE FULL CLINICAL

63
00:03:41,960 --> 00:03:43,600
 UTILITY.

64
00:03:43,600 --> 00:03:48,680
 ODS IS HAPPY TO BE JOINING

65
00:03:48,680 --> 00:03:49,840
 WITH NIEHS AND OTHER MEMBERS

66
00:03:49,840 --> 00:03:51,680
 OF THE WORKSHOP SO I WILL HAND

67
00:03:51,680 --> 00:03:55,200
 IT BACK TO DOCTOR KIM FOR THE

68
00:03:55,200 --> 00:03:56,440
 OTHER INTRODUCTIONS.

69
00:03:56,440 --> 00:03:57,400
 >> OKAY, THANK YOU.

70
00:03:57,400 --> 00:04:02,880
 SO IT IS MY HONOR TO INTRODUCE

71
00:04:02,880 --> 00:04:05,760
 OUR NEXT SPEAKER WHO WILL GIVE

72
00:04:05,760 --> 00:04:07,920
 A FEW WORDS TO TIP OFF THIS

73
00:04:07,920 --> 00:04:08,280
 WORKSHOP.

74
00:04:08,280 --> 00:04:15,920
 SO PLEASE JOIN ME IN WELCOMING

75
00:04:15,920 --> 00:04:16,320
 Dr. LANGEVIN.

76
00:04:16,320 --> 00:04:18,000
 >> HELLO, THANK YOU FOR

77
00:04:18,000 --> 00:04:20,520
 WELCOMING ME AND I AM HAPPY TO

78
00:04:20,520 --> 00:04:22,640
 BE PARTICIPATING IN THIS

79
00:04:22,640 --> 00:04:25,360
 WORKSHOP THAT HAS SUCH A

80
00:04:25,360 --> 00:04:26,240
 DIVERSE FIELD.

81
00:04:26,240 --> 00:04:28,600
 IT IS REALLY EXPANDIC AND THE

82
00:04:28,600 --> 00:04:31,600
 LINE BETWEEN CONVENTIONAL AND

83
00:04:31,600 --> 00:04:33,640
 COMPLIMENTARY APPROACHES IS

84
00:04:33,640 --> 00:04:39,080
 WORRYING AND THEREFORE, AT

85
00:04:39,080 --> 00:04:42,000
 NIH, WE FIND A WAY TO THINK

86
00:04:42,000 --> 00:04:44,360
 ABOUT THE THINGS WE SUPPORT IN

87
00:04:44,360 --> 00:04:47,120
 NEW CATEGORIES BASED ON THEIR

88
00:04:47,120 --> 00:04:48,960
 PRIMARY THERAPEUTIC INPUT SO I

89
00:04:48,960 --> 00:04:51,280
 WILL SHOW YOU A LITTLE VIDEO

90
00:04:51,280 --> 00:04:55,680
 TO SHOW YOU HOW THE PROBIOTICS

91
00:04:55,680 --> 00:04:57,720
 WILL FIT INTO THIS BIG

92
00:04:57,720 --> 00:05:00,080
 PICTURE.

93
00:05:00,080 --> 00:05:02,200
 SO YOU CAN SEE THIS IS WHAT WE

94
00:05:02,200 --> 00:05:07,200
 CALL OUR BUBBLE DIAGRAM AND

95
00:05:07,200 --> 00:05:10,480
 YOU CAN SEE THE THREE BIG,

96
00:05:10,480 --> 00:05:13,560
 SORT OF LARGE TYPES OF THE

97
00:05:13,560 --> 00:05:20,240
 DIFFERENT -- WHAT WE CALL THE 

98
00:05:20,240 --> 00:05:22,240
 THEIR PUTATIVE, NUTRITIONAL,

99
00:05:22,240 --> 00:05:22,920
 PSYCHOLOGICAL AND PHYSICAL.

100
00:05:22,920 --> 00:05:26,600
 AND YOU WILL SEE THESE BUBBLES

101
00:05:26,600 --> 00:05:28,240
 OVERLAP PARTIALLY TO INCLUDE

102
00:05:28,240 --> 00:05:29,800
 OTHER CATEGORIES, FOR EXAMPLE,

103
00:05:29,800 --> 00:05:31,120
 DRUGS AND DEVICES.

104
00:05:31,120 --> 00:05:35,440
 SO THIS ILLUSTRATES HOW THIS

105
00:05:35,440 --> 00:05:37,200
 PARTICULAR INSTANCE, HOW THE

106
00:05:37,200 --> 00:05:39,000
 CATEGORY OF NUTRITION INCLUDES

107
00:05:39,000 --> 00:05:41,280
 THINGS LIKE FOR EXAMPLE THE

108
00:05:41,280 --> 00:05:43,120
 DIET AND DIETARY PATTERN AND

109
00:05:43,120 --> 00:05:46,800
 IT ALSO INTERCEPTS WITH THE

110
00:05:46,800 --> 00:05:51,960
 PSYCHOLOGICAL CATEGORY, FOR

111
00:05:51,960 --> 00:06:00,400
 EXAMPLE, INTERVENTIONS THAT

112
00:06:00,400 --> 00:06:01,160
 PROMOTE MICROBES.

113
00:06:01,160 --> 00:06:03,080
 HERBS AND THINGS THAT ARE

114
00:06:03,080 --> 00:06:05,600
 PARTS OF A PERSON'S DIET AS

115
00:06:05,600 --> 00:06:07,240
 WELL AS OTHER PLANTS THAT ARE

116
00:06:07,240 --> 00:06:11,160
 NOT TAKEN AS PART OF DIET BUT

117
00:06:11,160 --> 00:06:15,000
 USED FOR MEDICINAL PURPOSES AS

118
00:06:15,000 --> 00:06:17,760
 WELL AS OTHER PRODUCTS SO YOU

119
00:06:17,760 --> 00:06:21,760
 SEE IT IS A DIVERSE FIELD AND

120
00:06:21,760 --> 00:06:23,800
 ALSO THE DIAGRAM SHOWS THE

121
00:06:23,800 --> 00:06:26,360
 SAME PRODUCT, FOR EXAMPLE,

122
00:06:26,360 --> 00:06:28,200
 NIACIN THAT CAN BE USED AS A

123
00:06:28,200 --> 00:06:29,720
 SUPPLEMENT BUT ALSO A

124
00:06:29,720 --> 00:06:30,640
 MEDICATION DEPENDING ON THE

125
00:06:30,640 --> 00:06:32,920
 DOSE THAT IS USED.

126
00:06:32,920 --> 00:06:38,600
 AND IT ALSO INCLUDES OF CORES

127
00:06:38,600 --> 00:06:44,000
 PROBIOTICS AND PREBIOTICS 

128
00:06:44,000 --> 00:06:51,040
 WHICH ARE CRUCIAL FOR THE

129
00:06:51,040 --> 00:06:53,120
 MICROBIAL AND INCLUDE PLANTS

130
00:06:53,120 --> 00:06:56,520
 AND HERBS AND THE POTENTIAL

131
00:06:56,520 --> 00:06:58,760
 INTERACTION BETWEEN THE SIMPLE

132
00:06:58,760 --> 00:06:59,880
 OR MULTIPLE BIOLOGICAL

133
00:06:59,880 --> 00:07:01,480
 SYSTEMS.

134
00:07:01,480 --> 00:07:03,080
 THIS IS PARTICULARLY IMPORTANT

135
00:07:03,080 --> 00:07:05,400
 FOCUSING ON WHAT WE CALL WHOLE

136
00:07:05,400 --> 00:07:07,640
 PERSON HEALTH WHICH MEANS THE

137
00:07:07,640 --> 00:07:09,920
 WAY WE DEFINE WHOLE PERSON

138
00:07:09,920 --> 00:07:11,400
 HEALTH IS EMPOWER INDIVIDUALS

139
00:07:11,400 --> 00:07:21,440
 TO IMPROVE THEIR HEALTH IN 

140
00:07:21,440 --> 00:07:24,840
 MULTIPLE DOMAINS, BEHAVIORAL,

141
00:07:24,840 --> 00:07:26,320
 BIOLOGICAL AND SOCIAL AND THE

142
00:07:26,320 --> 00:07:26,840
 WHOLE SYSTEM.

143
00:07:26,840 --> 00:07:28,680
 SO WE ARE PARTICULARLY

144
00:07:28,680 --> 00:07:30,240
 INTERESTED IN MULTISYSTEM

145
00:07:30,240 --> 00:07:37,680
 APPROACHES THAT TIE TOGETHER

146
00:07:37,680 --> 00:07:38,840
 VARIOUS AREAS THAT HELP WITH

147
00:07:38,840 --> 00:07:41,000
 HEALTH AND DISEASE PREVENTION.

148
00:07:41,000 --> 00:07:43,920
 THE WHOLE PERSON HEALTH

149
00:07:43,920 --> 00:07:47,600
 EMPHASIZES THE PATHWAY IS

150
00:07:47,600 --> 00:07:48,840
 BIODIRECTIONAL INCLUDING

151
00:07:48,840 --> 00:07:50,800
 APPROACHES TO LIFESTYLE AND

152
00:07:50,800 --> 00:07:52,600
 NUTRITION AND OTHER FACTORS

153
00:07:52,600 --> 00:07:54,800
 THAT CAN HELP AN INDIVIDUAL

154
00:07:54,800 --> 00:07:55,600
 RESTORE THEIR HEALTH.

155
00:07:55,600 --> 00:07:58,000
 SO I AM REALLY LOOKING FORWARD

156
00:07:58,000 --> 00:08:00,640
 TO THIS WORKSHOP WHICH WILL

157
00:08:00,640 --> 00:08:03,280
 INCLUDE MANY EXAMPLES OF THIS

158
00:08:03,280 --> 00:08:04,960
 TYPES OF RESEARCH INCLUDING

159
00:08:04,960 --> 00:08:08,600
 PATIENT SHALL AND TEMPORAL

160
00:08:08,600 --> 00:08:13,320
 DYNAMICS OF BIOLOGICAL 

161
00:08:13,320 --> 00:08:17,040
 ACTIVITY, PROBIOTICS, GI

162
00:08:17,040 --> 00:08:18,880
 TRACT, ESPECIALLY PROBIOTICS

163
00:08:18,880 --> 00:08:21,520
 LINKING THE GASTRO INTESTINAL

164
00:08:21,520 --> 00:08:25,800
 TRACT WITH THE BRAIN AND OTHER

165
00:08:25,800 --> 00:08:26,320
 IMPORTANT TOPICS.

166
00:08:26,320 --> 00:08:28,840
 SO THERE ARE A LOT OF

167
00:08:28,840 --> 00:08:30,360
 CHALLENGES STANDING IN THE WAY

168
00:08:30,360 --> 00:08:33,760
 OF PROGRESS IN FILLING THESE

169
00:08:33,760 --> 00:08:37,720
 GAPS AND OF COURSE WE WANT TO

170
00:08:37,720 --> 00:08:38,520
 PROVIDE A CLINICAL FOUNDATION

171
00:08:38,520 --> 00:08:39,680
 FOR FUTURE EFFORTS TO HAVE A

172
00:08:39,680 --> 00:08:40,000
 PRECISION PRO BY YACHTIC

173
00:08:40,000 --> 00:08:51,320
 THERAPY.

174
00:08:51,320 --> 00:08:52,840
 AND NOW I WILL TURN THINGS

175
00:08:52,840 --> 00:08:57,640
 OVER TO Dr. GABRIELA RISCUTA

176
00:08:57,640 --> 00:09:01,240
 FROM THE NATIONAL CANCER

177
00:09:01,240 --> 00:09:03,600
 INSTITUTE AND Dr. LUNSFORD

178
00:09:03,600 --> 00:09:07,440
 FROM THE NATIONAL INSTITUTE OF

179
00:09:07,440 --> 00:09:13,040
 DIABETES AND DIGESTIVE AND

180
00:09:13,040 --> 00:09:13,880
 KIDNEY DISEASE.

181
00:09:13,880 --> 00:09:15,960
 THEY WILL INTRODUCE THE

182
00:09:15,960 --> 00:09:17,560
 SESSION SPEAKERS AND SHARE THE

183
00:09:17,560 --> 00:09:19,640
 SLIDES SO NOW I WILL TURN

184
00:09:19,640 --> 00:09:22,360
 THINGS OVER TO Dr. LUNSFORD,

185
00:09:22,360 --> 00:09:25,000
 THANK YOU SO MUCH.

186
00:09:25,000 --> 00:09:26,240
 TAKE IT AWAY.

187
00:09:26,240 --> 00:09:31,880
 >> GOOD MORNING, EVERYONE, I'M

188
00:09:31,880 --> 00:09:33,640
 DWAYNE LUNSFORD, LIKE TO

189
00:09:33,640 --> 00:09:36,960
 WELCOME YOU TO SESSION 1, AND

190
00:09:36,960 --> 00:09:42,760
 AS A REMINDER, YOU CAN FIND 

191
00:09:42,760 --> 00:09:44,240
 FULL DETAILED SPEAKER

192
00:09:44,240 --> 00:09:45,280
 BIOGRAPHIES IN THE PROGRAM

193
00:09:45,280 --> 00:09:46,640
 BOOK.

194
00:09:46,640 --> 00:09:50,720
 OUR FIRST SPEAKER IS Dr.

195
00:09:50,720 --> 00:09:58,560
 RIMA WITH A SESSION CALLED 

196
00:09:58,560 --> 00:10:00,760
 METABOLOME GENOME GUT 

197
00:10:00,760 --> 00:10:01,880
 MICROBIOME DIET EXPOSOME

198
00:10:01,880 --> 00:10:02,280
 TOWARDS A PRECISION MEDICINE

199
00:10:02,280 --> 00:10:03,480
 APPROACH FOR PROBIOTIC

200
00:10:03,480 --> 00:10:04,920
 THERAPIES.

201
00:10:04,920 --> 00:10:05,040
YOUR AUDIO IS NOT WORKING

202
00:10:05,040 --> 00:10:14,560
 Dr. LUNSFORD, WOULD YOU GO?

203
00:10:14,560 --> 00:10:16,800
 >>I APPRECIATE

204
00:10:16,800 --> 00:10:20,440
 BEING INVITED 

205
00:10:20,440 --> 00:10:23,400
I HAVE BEEN ASKED TO SPEAK

206
00:10:23,400 --> 00:10:25,760
 WITH CLINICAL TRIALS.

207
00:10:25,760 --> 00:10:27,360
 I HAVE CLINICAL TRIALS I HAVE

208
00:10:27,360 --> 00:10:29,160
 BEEN DOING FOR 15 YEARS NOW

209
00:10:29,160 --> 00:10:30,920
 AND ALSO A PHYSICIANS SO I

210
00:10:30,920 --> 00:10:33,160
 BRING THAT TO THE HOUSE, TOO.

211
00:10:33,160 --> 00:10:35,160
 I HAVE BEEN A PAID CONSULTANT 

212
00:10:35,160 --> 00:10:37,560
 FOR HOWARU AND ANOTHER PAID

213
00:10:37,560 --> 00:10:39,480
 POSITION.

214
00:10:39,480 --> 00:10:42,320
 SO I WAS SPECIFICALLY ASKED TO

215
00:10:42,320 --> 00:10:45,720
 COVER THE CHALLENGES FACED

216
00:10:45,720 --> 00:10:46,880
 DURING PROBIOTIC CLINICAL

217
00:10:46,880 --> 00:10:49,720
 TRIALS DUE TO DIFFERENT

218
00:10:49,720 --> 00:10:50,720
 RESPONSES TO PROBIOTIC

219
00:10:50,720 --> 00:10:52,320
 INTERVENTIONS AND HOW TO

220
00:10:52,320 --> 00:10:54,520
 IMPROVE THE RESPONSIVENESS IN

221
00:10:54,520 --> 00:10:56,560
 THE CLINICAL SETTING.

222
00:10:56,560 --> 00:10:59,320
 I TRANSLATED THIS AS SUCH AND

223
00:10:59,320 --> 00:11:01,400
 SO MY OBJECTIVES WILL BE TO

224
00:11:01,400 --> 00:11:02,720
 REVIEW HOW CLINICAL TRIALS ARE

225
00:11:02,720 --> 00:11:05,120
 CARRIED OUT AND ANALYZED,

226
00:11:05,120 --> 00:11:05,920
 UNDERSTAND WHAT WE ARE

227
00:11:05,920 --> 00:11:07,920
 ACTUALLY REQUIRED TO DO IN

228
00:11:07,920 --> 00:11:08,960
 CLINICAL RESEARCH, HELP US TO

229
00:11:08,960 --> 00:11:10,040
 CONSIDER WHAT NEEDS TO BE DONE

230
00:11:10,040 --> 00:11:13,760
 TO GET TO CLINICAL TRIALS IN

231
00:11:13,760 --> 00:11:15,760
 PROBIOTICS. 

232
00:11:15,760 --> 00:11:16,480
 MOST COMMON REASONS

233
00:11:16,480 --> 00:11:18,280
 INTERVENTION DOES NOT WORK IS

234
00:11:18,280 --> 00:11:21,120
 YOUR STRAIN HAS LIMITED TO NO

235
00:11:21,120 --> 00:11:21,520
 EFFICACY.

236
00:11:21,520 --> 00:11:23,280
 OR YOUR STRAIN DOESN'T WORK

237
00:11:23,280 --> 00:11:25,560
 FOR THAT INDIVIDUAL, FOR THAT

238
00:11:25,560 --> 00:11:28,880
 INDICATION OR AGE, SEX OR

239
00:11:28,880 --> 00:11:29,520
 DIET.

240
00:11:29,520 --> 00:11:32,560
 I WILL SAY IN SPECIFIC

241
00:11:32,560 --> 00:11:33,360
 PROBIOTIC TRIALS, TIMING SEEMS

242
00:11:33,360 --> 00:11:34,400
 TO BE ESPECIALLY IMPORTANT.

243
00:11:34,400 --> 00:11:37,400
 THIS IS A REALLY NICE STUDY BY

244
00:11:37,400 --> 00:11:43,120
 Dr. ALLEN THAT LOOKED AT

245
00:11:43,120 --> 00:11:43,720
 ANTIBIOTIC-ASSOCIATED

246
00:11:43,720 --> 00:11:49,120
 DIARRHEA, ONE OF THE FEW AND

247
00:11:49,120 --> 00:11:51,560
 IT STARTED ON PEOPLE AVERAGE

248
00:11:51,560 --> 00:11:52,760
 3-7 DAYS.

249
00:11:52,760 --> 00:11:54,720
 WE TRY TO START IT IMMEDIATELY

250
00:11:54,720 --> 00:11:56,520
 AND OTHERS HAVE DONE THE SAME

251
00:11:56,520 --> 00:11:58,680
 WITH A BETTER OUTCOME SO IT

252
00:11:58,680 --> 00:12:01,320
 HAS BEEN SEEN THAT WITH

253
00:12:01,320 --> 00:12:02,120
 CERTAIN ANTIBIOTICS, YOU DO

254
00:12:02,120 --> 00:12:03,520
 NEED TO TIME THE SUPPORT.

255
00:12:03,520 --> 00:12:08,200
 HOW DO WE LOOK AT THE DATA IN

256
00:12:08,200 --> 00:12:10,200
 CLINICAL FORM, AND HOW DOES

257
00:12:10,200 --> 00:12:12,000
 ONE DO THIS?

258
00:12:12,000 --> 00:12:14,400
 EXAMINING CLINICAL TRIALS IS

259
00:12:14,400 --> 00:12:15,800
 VERY DIFFERENT THAN BENCH

260
00:12:15,800 --> 00:12:17,640
 RESEARCH LOOKING FOR

261
00:12:17,640 --> 00:12:19,160
 SIGNIFICANT FINDINGS AND HERE

262
00:12:19,160 --> 00:12:23,720
 IS A STATEMENT BY THE STUDENT.

263
00:12:23,720 --> 00:12:27,160
 [ READING FROM SLIDE ]

264
00:12:27,160 --> 00:12:28,280
 WE TESTED DIFFERENT VARIABLES

265
00:12:28,280 --> 00:12:29,640
 ON A PROMOTER GENE THAT COULD

266
00:12:29,640 --> 00:12:32,200
 BE LOCKED ON TO DETERMINE IF

267
00:12:32,200 --> 00:12:34,600
 WE COULD REDUCE INFLAMMATION

268
00:12:34,600 --> 00:12:36,560
 IN PEOPLE WITH INFAMILIAR TORE

269
00:12:36,560 --> 00:12:37,200
 BOWEL DISEASE.

270
00:12:37,200 --> 00:12:38,560
 WE TESTED A VARIETY OF

271
00:12:38,560 --> 00:12:40,160
 DIFFERENT FACTORS ON THE GENE

272
00:12:40,160 --> 00:12:42,600
 THROUGHOUT THE SUMMER BUT NOT

273
00:12:42,600 --> 00:12:43,800
 SINGLE FACTOR SIGNIFICANTLY

274
00:12:43,800 --> 00:12:44,480
 ALTERED THE GENE.

275
00:12:44,480 --> 00:12:47,480
 ON THE FINAL DAY OF THE WEEK

276
00:12:47,480 --> 00:12:50,760
 8, I FINAL LIE FOUND A

277
00:12:50,760 --> 00:12:53,200
 VARIABLE THAT SIGNIFICANTLY

278
00:12:53,200 --> 00:12:53,960
 ALTERED IT.

279
00:12:53,960 --> 00:12:55,360
 SO THE ANALYSIS WAS TOTALLY

280
00:12:55,360 --> 00:12:56,560
 DIFFERENT THAN WHAT HE DID.

281
00:12:56,560 --> 00:12:58,680
 SO WE LOOK AT THE PRIMARY

282
00:12:58,680 --> 00:12:59,160
 OUTCOME MEASURES.

283
00:12:59,160 --> 00:13:00,640
 THIS IS THE STUDY I WILL TALK

284
00:13:00,640 --> 00:13:02,840
 TO YOU AND SHOW YOU SOME DATA

285
00:13:02,840 --> 00:13:05,840
 AND WHAT WE DID WAS TO LIST

286
00:13:05,840 --> 00:13:06,920
 THE PRIMARY OUTCOME AND

287
00:13:06,920 --> 00:13:07,280
 SECONDARY.

288
00:13:07,280 --> 00:13:11,720
 THIS IS THE PRIME CARE

289
00:13:11,720 --> 00:13:13,520
 OUTCOME, CHANGE FROM BASELINE

290
00:13:13,520 --> 00:13:17,840
 LEVELS OF FECAL SHORT-CHAIN

291
00:13:17,840 --> 00:13:20,400
 FATTY ACID WITH PARTICULAR

292
00:13:20,400 --> 00:13:22,840
 FOCUS ON ACETATE AND THEN

293
00:13:22,840 --> 00:13:26,520
 CHANGE FROM BASELINE LEVELS OF

294
00:13:26,520 --> 00:13:31,280
 FECAL SHORT-CHAIN FATTY ACID

295
00:13:31,280 --> 00:13:34,000
 WITH PARTICULAR FOCUS ON DAY

296
00:13:34,000 --> 00:13:34,680
 30.

297
00:13:34,680 --> 00:13:41,160
 SO WE LOOKED AT A NUMBER OF

298
00:13:41,160 --> 00:13:42,760
 MICROBIOTA PIECE SEES AND THIS

299
00:13:42,760 --> 00:13:44,640
 IS WHAT EVERYONE IN A CLINICAL

300
00:13:44,640 --> 00:13:47,160
 TRIAL IS REQUIRED TO DO, EVERY

301
00:13:47,160 --> 00:13:48,360
 REVIEWER OR EDITOR LOOKS TO

302
00:13:48,360 --> 00:13:50,320
 SEE THAT THIS IS DONE.

303
00:13:50,320 --> 00:13:53,560
 SO THAT IS OUR PRIMARY

304
00:13:53,560 --> 00:13:56,760
 OUTCOMES AND THERE ARE SOME

305
00:13:56,760 --> 00:14:01,280
 OTHERS ON THE LIST BUT WHAT

306
00:14:01,280 --> 00:14:04,600
 HAPPENS IF WE FOUND ACETATE

307
00:14:04,600 --> 00:14:09,880
 HAD NO CHANGE OR IF IT WAS

308
00:14:09,880 --> 00:14:11,240
 IMPACTED BY INTERVENTION OR IF

309
00:14:11,240 --> 00:14:14,760
 IT WAS CHANGED AT DAY 14 OR 21

310
00:14:14,760 --> 00:14:15,920
 BUT NOT DAY 7?

311
00:14:15,920 --> 00:14:21,040
 AND THEN THE OTHER  OUTCOMES,

312
00:14:21,040 --> 00:14:23,720
 A CHANGE IN REPORTED SYMPTOMS

313
00:14:23,720 --> 00:14:26,640
 AND WHAT IF WE FOUND KIDS WHO

314
00:14:26,640 --> 00:14:29,040
 TOOK THE PROBIOTIC

315
00:14:29,040 --> 00:14:29,880
 SIGNIFICANTLY MISSED LESS

316
00:14:29,880 --> 00:14:30,320
 SCHOOL?

317
00:14:30,320 --> 00:14:32,480
 SO THIS IS VERY IMPORTANT ON

318
00:14:32,480 --> 00:14:34,200
 THE TRIALS WITH PRECISION

319
00:14:34,200 --> 00:14:36,160
 METRICS AND THE REASON WE DO

320
00:14:36,160 --> 00:14:38,240
 THAT OR ONE OF THE REASONS IS

321
00:14:38,240 --> 00:14:42,200
 WE NEED A LIST AHEAD OF TIME

322
00:14:42,200 --> 00:14:44,200
 SO WE CAN CHAIN TO DATA MINE.

323
00:14:44,200 --> 00:14:46,040
 SO WHERE WE REPORT THIS WHEN

324
00:14:46,040 --> 00:14:48,560
 WE REPORT OUR TRIALS IS THE

325
00:14:48,560 --> 00:14:49,000
 CHECKLIST.

326
00:14:49,000 --> 00:14:53,360
 SO PEOPLE WHO NOT DONE

327
00:14:53,360 --> 00:14:55,440
 CLINICAL TRIALS, THERE ARE

328
00:14:55,440 --> 00:15:00,400
 CHECK LISTS YOU HAVE TO SHOW

329
00:15:00,400 --> 00:15:02,040
 IN JOURNALS WHERE YOU SPEND

330
00:15:02,040 --> 00:15:08,040
 ANY TIME TALKING ABOUT IT.

331
00:15:08,040 --> 00:15:08,960
 WHICH IS THIS.

332
00:15:08,960 --> 00:15:10,240
 [ READING FROM SLIDE ]

333
00:15:10,240 --> 00:15:21,800
 SO THIS NEEDS TO BE LISTED AND

334
00:15:21,800 --> 00:15:22,480
 IF YOU HAD MAJOR CHANGES OR

335
00:15:22,480 --> 00:15:23,120
 DON'T LIST YOUR PRIMARY OR

336
00:15:23,120 --> 00:15:23,720
 SECONDARY OUTCOMES, A GOOD

337
00:15:23,720 --> 00:15:24,320
 JOURNAL WILL REJECT YOUR

338
00:15:24,320 --> 00:15:24,720
 RESEARCH.

339
00:15:24,720 --> 00:15:25,360
 SO WHAT HAVE WE DONE IN THE

340
00:15:25,360 --> 00:15:26,040
 PAST TO IDENTIFY RESPONDERS?

341
00:15:26,040 --> 00:15:26,960
 WELL, INCLUSION/EXCLUSION IS

342
00:15:26,960 --> 00:15:28,840
 USED FOR SAFETY BUT ALSO TO

343
00:15:28,840 --> 00:15:31,600
 HELP FIND WHO BENEFITS SO WE

344
00:15:31,600 --> 00:15:33,120
 HAVE EXCLUDED ELDERLY OR

345
00:15:33,120 --> 00:15:35,520
 INFANTS, PEOPLE WHO HAVE

346
00:15:35,520 --> 00:15:37,480
 CERTAIN DIETS, ONLY

347
00:15:37,480 --> 00:15:38,760
 HOSPITALIZED PATIENTS, WE HAVE

348
00:15:38,760 --> 00:15:41,440
 BEEN DOING THAT FOR YEAR.

349
00:15:41,440 --> 00:15:42,560
 SO CLINICAL RESEARCHERS HAVE

350
00:15:42,560 --> 00:15:44,320
 ALWAYS TRIED TO FIND

351
00:15:44,320 --> 00:15:46,840
 RESPONDERS, IN THE PAST CALLED

352
00:15:46,840 --> 00:15:49,520
 DATA MINING, NOW WE CALL IT

353
00:15:49,520 --> 00:15:54,000
 PREDICTIVE ANALYTICS, MACHINE 

354
00:15:54,000 --> 00:15:54,640
 LEARNING, DATA ANALYTICS,

355
00:15:54,640 --> 00:15:55,200
 ALGORITHMS, ET CETERA.

356
00:15:55,200 --> 00:15:58,200
 BUT THE PROBLEM IS YOU ARE

357
00:15:58,200 --> 00:16:01,520
 LOOKING AT SOMETHING THAT

358
00:16:01,520 --> 00:16:03,000
 COULD DIFFER SIGNIFICANTLY BUT

359
00:16:03,000 --> 00:16:04,520
 DOESN'T ANSWER THE QUESTION.

360
00:16:04,520 --> 00:16:06,600
 THE MORE TESTS ONE RUNS, THEY

361
00:16:06,600 --> 00:16:08,440
 ARE LIKELY TO SEE AN EFFECT

362
00:16:08,440 --> 00:16:10,280
 AND ONE CAN EASILY MISTAKE

363
00:16:10,280 --> 00:16:12,360
 THAT FOR A TRUE FINDING.

364
00:16:12,360 --> 00:16:15,520
 THIS CAN RESULT IN A P VALUE

365
00:16:15,520 --> 00:16:20,600
 AT 0.05 LEVEL OF STATISTICAL

366
00:16:20,600 --> 00:16:21,080
 SIGNIFICANCE.

367
00:16:21,080 --> 00:16:22,720
 AND WHAT ONE CAN AND SHOULD DO

368
00:16:22,720 --> 00:16:25,560
 IS CHANGE THEIR P VALUE FOR

369
00:16:25,560 --> 00:16:27,360
 THIS BUT PAY ATTENTION TO HOW

370
00:16:27,360 --> 00:16:28,560
 THEY DO THAT.

371
00:16:28,560 --> 00:16:38,480
 HERE IS A CARTOON DOCUMENT 

372
00:16:38,480 --> 00:16:40,480
 WHERE JELLY BEANS CAUSING

373
00:16:40,480 --> 00:16:42,520
 THAT, IT WORKS ALL THE WAY

374
00:16:42,520 --> 00:16:45,320
 THROUGH AND SAY GREEN JELLY

375
00:16:45,320 --> 00:16:47,480
 BEANS CAUSE ACNE AND WE SEE

376
00:16:47,480 --> 00:16:48,920
 THIS RESEARCH ALL THE TIME

377
00:16:48,920 --> 00:16:52,360
 ESPECIALLY LEAP IN THE LAY

378
00:16:52,360 --> 00:16:53,400
 TRANSFER TALKING ABOUT COPY

379
00:16:53,400 --> 00:16:54,800
 AND THINGS LIKE THAT, ALWAYS

380
00:16:54,800 --> 00:16:59,520
 GETS A LOT OF PRESS BUT REALLY

381
00:16:59,520 --> 00:17:04,520
 WHAT ONE NEEDS TO ASK IS, IS

382
00:17:04,520 --> 00:17:10,720
 THIS AN OUTCOME OR DATA

383
00:17:10,720 --> 00:17:11,080
 MINING?

384
00:17:11,080 --> 00:17:14,080
 SO MULTIPLE OUTCOMES IN

385
00:17:14,080 --> 00:17:18,280
 PERSONALIZED MEDICINE, A STUDY

386
00:17:18,280 --> 00:17:23,320
 REGISTERED AND THE PRIMARY 

387
00:17:23,320 --> 00:17:25,680
 OUTCOME LIFTED ON MICROBIOME,

388
00:17:25,680 --> 00:17:27,520
 STOOL AND ORAL SAMPLES, TIME

389
00:17:27,520 --> 00:17:28,880
 FRAME ONE YEAR.

390
00:17:28,880 --> 00:17:30,680
 DOES THIS MEAN THERE IS ANY

391
00:17:30,680 --> 00:17:32,320
 CHANGE AT ALL ANY TIME OF THE

392
00:17:32,320 --> 00:17:37,920
 YEAR THAT IS A SUCCESS OR WHAT

393
00:17:37,920 --> 00:17:39,040
 CHANGES THE MICROBIOME?

394
00:17:39,040 --> 00:17:40,760
 WELL, IF PEOPLE ARE BETTER IN

395
00:17:40,760 --> 00:17:42,840
 DAY 7 BUT NOT BETTER IN DAY 3,

396
00:17:42,840 --> 00:17:49,120
 I HAD A NEGATIVE STUDY SO THIS

397
00:17:49,120 --> 00:17:51,400
 LOOKS LIKE SOMEONE WHO IS A

398
00:17:51,400 --> 00:17:53,120
 BENCH RESEARCHER TRYING TO DO

399
00:17:53,120 --> 00:17:54,080
 CLINICAL STUDIES AND

400
00:17:54,080 --> 00:17:57,520
 EVERYTHING IS FINE AT THE

401
00:17:57,520 --> 00:18:00,160
 BEGINNING BUT AS IT GOES

402
00:18:00,160 --> 00:18:00,960
 THROUGH, WITH DIFFERENT

403
00:18:00,960 --> 00:18:01,320
 EFFECTS.

404
00:18:01,320 --> 00:18:08,240
 SO THIS IS A STUDY WE TALKED

405
00:18:08,240 --> 00:18:11,400
 ABOUT BEFORE, AND YOU CAN SEE

406
00:18:11,400 --> 00:18:13,920
 PROBIOTICS, SOME PEOPLE GOT

407
00:18:13,920 --> 00:18:15,320
 THEM, SOME WHO GOT CONTROL

408
00:18:15,320 --> 00:18:17,920
 NEVER GOT UP TO THE ACETATE

409
00:18:17,920 --> 00:18:20,520
 BUT PEOPLE WHO GOT THE ACTIVE,

410
00:18:20,520 --> 00:18:22,480
 THEY GOT BACK TO DAY 1 SO WE

411
00:18:22,480 --> 00:18:24,960
 TRY TO LOOK AT THE MECHANISM

412
00:18:24,960 --> 00:18:27,640
 AND WE ALSO DID THE MICROBIOME

413
00:18:27,640 --> 00:18:29,520
 DATA BUT I WANTED TO TALK

414
00:18:29,520 --> 00:18:30,720
 ABOUT THIS BECAUSE IT IS A

415
00:18:30,720 --> 00:18:31,560
 NICE EXAMPLE.

416
00:18:31,560 --> 00:18:35,120
 YOU SEE THIS LOOKS REALLY

417
00:18:35,120 --> 00:18:35,760
 NICE.

418
00:18:35,760 --> 00:18:38,760
 REALLY HAPPY ABOUT THIS, GOING

419
00:18:38,760 --> 00:18:41,120
 FROM R-32 TO R-33, VERY

420
00:18:41,120 --> 00:18:42,800
 POSITIVE BUT THEN LOOK HERE.

421
00:18:42,800 --> 00:18:44,520
 THIS IS GROUP DATA BUT IF YOU

422
00:18:44,520 --> 00:18:46,760
 ACTUALLY LOOK AT THE RAW DATA,

423
00:18:46,760 --> 00:18:48,720
 SOME PEOPLE DID BETTER, SOME

424
00:18:48,720 --> 00:18:50,480
 PEOPLE DID WORSE BUT THAT IS

425
00:18:50,480 --> 00:18:53,720
 NOT HOW IT WAS REPORTED IN

426
00:18:53,720 --> 00:18:54,880
 CRITICAL MEDICINE.

427
00:18:54,880 --> 00:18:57,840
 WE WEREN'T TRYING TO HIDE IT,

428
00:18:57,840 --> 00:18:59,480
 THIS JUST LOOKS BETTER.

429
00:18:59,480 --> 00:19:01,880
 BUT AGAIN SOME PEOPLE DID

430
00:19:01,880 --> 00:19:04,360
 BETTER, SOME PEOPLE DID WORSE

431
00:19:04,360 --> 00:19:06,680
 BUT YOU CAN'T TELL HOW OR WHY

432
00:19:06,680 --> 00:19:08,840
 SOME PEOPLE DID BETTER THAN

433
00:19:08,840 --> 00:19:09,200
 OTHERS.

434
00:19:09,200 --> 00:19:11,920
 SO PERSONAL I.C.E.D MEDICINE

435
00:19:11,920 --> 00:19:13,960
 IN MY OPINION BY DEFINITION

436
00:19:13,960 --> 00:19:15,240
 WOULD MEAN INDIVIDUAL DATA BUT

437
00:19:15,240 --> 00:19:17,440
 AGAIN, HOW WE ARE REQUIRED TO

438
00:19:17,440 --> 00:19:18,920
 REPORT CLINICAL TRIALS IS BY

439
00:19:18,920 --> 00:19:22,160
 GROUP SO AGAIN, THIS IS THE

440
00:19:22,160 --> 00:19:24,760
 CONSORTYOU SEE HERE, THE

441
00:19:24,760 --> 00:19:30,520
 STATIVITY  -- STATISTICAL

442
00:19:30,520 --> 00:19:33,320
 METHOD USED TO REPORT FOR EACH

443
00:19:33,320 --> 00:19:35,080
 GROUP BUT NO ONE LOOKS BACK

444
00:19:35,080 --> 00:19:37,040
 HERE AND SAYS LET'S FIGURE OUT

445
00:19:37,040 --> 00:19:38,800
 WHY THIS PERSON IS HERE, THIS

446
00:19:38,800 --> 00:19:39,920
 PERSON IS HERE.

447
00:19:39,920 --> 00:19:42,680
 IT IS NOT HOW THIS IS

448
00:19:42,680 --> 00:19:43,120
 REPORTED.

449
00:19:43,120 --> 00:19:45,200
 OKAY, ONE EXTRA CHALLENGE I

450
00:19:45,200 --> 00:19:47,400
 FIND IN DOING A STUDY FOR PRO

451
00:19:47,400 --> 00:19:49,520
 BY YACHT TICK TRIALS IS DIET.

452
00:19:49,520 --> 00:19:52,320
 DIET IS REALLY A HARD THING IN

453
00:19:52,320 --> 00:19:53,720
 PROBIOTIC TRIALS.

454
00:19:53,720 --> 00:19:55,760
 AGAIN, WE'RE NOT IN

455
00:19:55,760 --> 00:19:57,040
 LABORATORIES, CAN'T CONTROL

456
00:19:57,040 --> 00:19:57,960
 PEOPLE'S DIET AND EVERYONE

457
00:19:57,960 --> 00:20:03,920
 COMES TO US WITH DIFFERENT 

458
00:20:03,920 --> 00:20:05,560
 DIETS AND MICROBIOMES.

459
00:20:05,560 --> 00:20:08,080
 AND IN HUMANS, THAT IS REALLY

460
00:20:08,080 --> 00:20:08,400
 COMPLEX.

461
00:20:08,400 --> 00:20:10,920
 THIS IS A REAL LIE NICE STUDY.

462
00:20:10,920 --> 00:20:16,880
 I LIKE THIS STUDY, YOU HAVE 36

463
00:20:16,880 --> 00:20:19,000
 PEOPLE TOTAL, 18 IN EACH

464
00:20:19,000 --> 00:20:22,280
 GROUP, SOME FED A HIGH FIBER

465
00:20:22,280 --> 00:20:24,680
 DIET, THE OTHERS A HIGH

466
00:20:24,680 --> 00:20:26,320
 FERMENTED FOOD DIET AND YOU

467
00:20:26,320 --> 00:20:30,400
 CAN SEE THIS INCREASED

468
00:20:30,400 --> 00:20:34,040
 MICROBIOME FUNCTION, THIS 

469
00:20:34,040 --> 00:20:36,400
 INCREASED THE DIVERSITY AND

470
00:20:36,400 --> 00:20:45,800
 THE OUTCOME BUT AGAIN, A

471
00:20:45,800 --> 00:20:47,920
 36-PERSON RANDOM STUDY, THEY

472
00:20:47,920 --> 00:20:50,440
 WERE LOOKED AT FOR THREE DAYS

473
00:20:50,440 --> 00:20:52,080
 FOR NINE DIFFERENT TIME POINTS

474
00:20:52,080 --> 00:20:54,160
 AND 27 DAYS OUT OF 70 DAYS OF

475
00:20:54,160 --> 00:20:55,760
 INTERVENTION SO THINK IF YOU

476
00:20:55,760 --> 00:20:58,320
 HAVE BEEN A PART OF A TRIAL,

477
00:20:58,320 --> 00:21:00,720
 FOR 27 DAYS THEY LOGGED ALL

478
00:21:00,720 --> 00:21:02,560
 THEIR FOOD AND DRINK INTAKE

479
00:21:02,560 --> 00:21:04,640
 FOR THREE DAYS, TWO WEEKDAYS

480
00:21:04,640 --> 00:21:06,920
 AND ONE WEEKEND, EACH WEEK

481
00:21:06,920 --> 00:21:07,920
 DURING THE RAMP PHASE AND

482
00:21:07,920 --> 00:21:13,120
 EVERY WEEK FOR THE REST OF THE

483
00:21:13,120 --> 00:21:14,600
 STUDY USING HEALTHWATCH360

484
00:21:14,600 --> 00:21:16,120
 APP.

485
00:21:16,120 --> 00:21:18,880
 SO THE DIETICIAN REVIEWED THE

486
00:21:18,880 --> 00:21:20,520
 ENTRIES WITH PARTICIPANTS TO

487
00:21:20,520 --> 00:21:23,240
 ASSESS ACCURACY OF ENTRIES AND

488
00:21:23,240 --> 00:21:23,600
 PORTIONS.

489
00:21:23,600 --> 00:21:25,280
 ON AVERAGE OF THE THREE DAYS

490
00:21:25,280 --> 00:21:28,480
 USED FOR EACH TIME POINT,

491
00:21:28,480 --> 00:21:30,520
 ENTRIES FOR TIME POINTS

492
00:21:30,520 --> 00:21:33,880
 BASELINE WEEK 4, WEEK 10, WEEK

493
00:21:33,880 --> 00:21:35,920
 14 WERE REENTERED INTO THE

494
00:21:35,920 --> 00:21:37,880
 NUTRITION DATA SYSTEM FOR

495
00:21:37,880 --> 00:21:38,360
 RESEARCH DATABASE.

496
00:21:38,360 --> 00:21:40,120
 THIS WAS A GREAT STUDY BUT

497
00:21:40,120 --> 00:21:43,400
 THINK ABOUT HOW MUCH TIME WAS

498
00:21:43,400 --> 00:21:43,920
 SPENT.

499
00:21:43,920 --> 00:21:48,520
 THINK ABOUT THAT WHEN YOU ARE

500
00:21:48,520 --> 00:21:49,800
 DOING YOUR NIH STUDIES, IT

501
00:21:49,800 --> 00:21:51,920
 TAKES A LOT OF TIME BUT IT IS

502
00:21:51,920 --> 00:21:53,520
 REAL IMPORTANT WE HAVE THE

503
00:21:53,520 --> 00:21:55,160
 DIET DATA AND MOST OF THEM ARE

504
00:21:55,160 --> 00:21:58,920
 NOT GOING TO HAVE ANY LIKE

505
00:21:58,920 --> 00:22:00,800
 THIS KIND OF DATA.

506
00:22:00,800 --> 00:22:03,680
 SO A FEW POINTS, NUMBER NEEDED

507
00:22:03,680 --> 00:22:05,720
 TO TREAT, PROBABLY THE MOST

508
00:22:05,720 --> 00:22:07,240
 COMMON NUMBER WE USE, THE

509
00:22:07,240 --> 00:22:08,640
 AVERAGE NUMBER OF PATIENTS WHO

510
00:22:08,640 --> 00:22:09,720
 NEED TO RECEIVE THE TREATMENT

511
00:22:09,720 --> 00:22:12,200
 FOR ONE OF THEM TO GET THE

512
00:22:12,200 --> 00:22:14,600
 POSITIVE OUTCOME IN TIME

513
00:22:14,600 --> 00:22:14,960
 SPECIFIED.

514
00:22:14,960 --> 00:22:16,720
 >> YOU HAVE JUST A COUPLE

515
00:22:16,720 --> 00:22:17,800
 MINUTES LEFT, THANKS.

516
00:22:17,800 --> 00:22:19,360
 >> OKAY, NO PROBLEM.

517
00:22:19,360 --> 00:22:22,520
 SO THE PROBIOTIC A PREVENTS

518
00:22:22,520 --> 00:22:24,400
 COVID DEATH BY 75 PERCENT BUT

519
00:22:24,400 --> 00:22:27,160
 THE PLACEBO ALSO PREVENTS

520
00:22:27,160 --> 00:22:28,600
 DEATH BY 25 PERCENT, THAT

521
00:22:28,600 --> 00:22:30,720
 MEANS 25 PERCENT OF THE PEOPLE

522
00:22:30,720 --> 00:22:36,080
 DIDN'T NEED TO DIE AND THE 

523
00:22:36,080 --> 00:22:39,240
 STUDY IS AMAZING.

524
00:22:39,240 --> 00:22:40,960
 SO STATINS, THE MEDICATION YOU

525
00:22:40,960 --> 00:22:50,120
 ARE ON, ONE IN 217 AVOIDED

526
00:22:50,120 --> 00:22:51,520
 NONFATAL MYOCARDIAL

527
00:22:51,520 --> 00:22:57,320
 INFARCTION, 1 IN 313 AVOIDED

528
00:22:57,320 --> 00:22:58,880
 NONNATAL STROKE.

529
00:22:58,880 --> 00:23:00,360
 PASSENGERSLY AT HIGH LEVELS

530
00:23:00,360 --> 00:23:02,040
 POSSIBLE FOR CROSSOVER TRIAL,

531
00:23:02,040 --> 00:23:06,920
 STILL ANALYZED AS A GROUP BUT 

532
00:23:06,920 --> 00:23:09,160
 THE PARTICIPANTS ENVIRONMENT,

533
00:23:09,160 --> 00:23:13,760
 DIET, HOW IT WASHES OUT, SO WE

534
00:23:13,760 --> 00:23:15,960
 DID A SHORT-TERM STUDY OF A

535
00:23:15,960 --> 00:23:22,320
 DAILY INTAKE OF YOGURT

536
00:23:22,320 --> 00:23:22,920
 CONTAINING BF-6.

537
00:23:22,920 --> 00:23:24,600
 IF WE STOPPED THE TRIAL BEFORE

538
00:23:24,600 --> 00:23:26,680
 THE CROSSOVER, WE HAD A

539
00:23:26,680 --> 00:23:29,160
 POSITIVE STUDY SO SOMETHING

540
00:23:29,160 --> 00:23:29,920
 PROBABLY HAPPENED WITH THE

541
00:23:29,920 --> 00:23:33,160
 GROUPS THAT HAD THE CHANGE IN

542
00:23:33,160 --> 00:23:35,520
 THE MICROBIOME LONG-TERM, SO

543
00:23:35,520 --> 00:23:38,720
 YOU THINK ABOUT THAT OVER THE

544
00:23:38,720 --> 00:23:40,600
 TRIAL, HARD TO GET THE FULL

545
00:23:40,600 --> 00:23:40,920
 DATA.

546
00:23:40,920 --> 00:23:42,560
 HOPEFULLY I HAVE CONVINCED YOU

547
00:23:42,560 --> 00:23:45,120
 THAT ARE YOUR STANDARD WAY OF

548
00:23:45,120 --> 00:23:46,720
 DOING CLINICAL TRIALS CAN

549
00:23:46,720 --> 00:23:47,920
 REALLY LIMIT THE INFORMATION

550
00:23:47,920 --> 00:23:49,120
 WE GLEAN ABOUT INDIVIDUAL

551
00:23:49,120 --> 00:23:50,280
 RESPONSES, OUR ANALYSIS IS

552
00:23:50,280 --> 00:23:55,120
 BASED ON GROUP AGGREGATES AND

553
00:23:55,120 --> 00:23:55,840
 MASKS INDIVIDUAL RESPONSES,

554
00:23:55,840 --> 00:23:57,800
 AND REQUIREMENT FOR SETTING UP

555
00:23:57,800 --> 00:24:03,560
 THE TRIAL WITH A PRIORI

556
00:24:03,560 --> 00:24:05,160
 ESTABLISHMENT OF SUCCESS,

557
00:24:05,160 --> 00:24:06,840
 KEEPS THE CLINICAL TRIALIST

558
00:24:06,840 --> 00:24:09,520
 FROM FISHING THROUGH A TON OF

559
00:24:09,520 --> 00:24:10,560
 DATA.

560
00:24:10,560 --> 00:24:11,520
 THIS SHOULD BE DIFFICULT AND I

561
00:24:11,520 --> 00:24:12,920
 THINK I WILL SKIP THIS AND I

562
00:24:12,920 --> 00:24:14,320
 THINK WE NEED TO TALK ABOUT

563
00:24:14,320 --> 00:24:16,320
 HOW WE MOVE FORWARD WITH

564
00:24:16,320 --> 00:24:18,120
 LIMITATIONS, HOW WE INTERPRET

565
00:24:18,120 --> 00:24:20,120
 THE FINDINGS BEING REPORTED

566
00:24:20,120 --> 00:24:21,880
 AND RETHINK ABOUT HOW WE

567
00:24:21,880 --> 00:24:25,080
 ENROLL AND ANALYZE IN ORDER TO

568
00:24:25,080 --> 00:24:26,600
 DO PRECISION MEDICINE CLINICAL

569
00:24:26,600 --> 00:24:26,920
 TRIALS.

570
00:24:26,920 --> 00:24:28,560
 THANK YOU FOR YOUR TIME AND I

571
00:24:28,560 --> 00:24:30,760
 WILL CREDE TO THE NEXT

572
00:24:30,760 --> 00:24:31,200
 SPEAKER.

573
00:24:31,200 --> 00:24:32,520
 >> THANKS, DAN, THANKS FOR

574
00:24:32,520 --> 00:24:33,600
 STEPPING IN OUT OF ORDER AND I

575
00:24:33,600 --> 00:24:35,320
 AM SURE THERE WILL BE REALLY

576
00:24:35,320 --> 00:24:37,320
 GREAT QUESTIONS LATER ON.

577
00:24:37,320 --> 00:24:38,760
 WE HAVE RIMA BACK?

578
00:24:38,760 --> 00:24:40,320
 >> CAN YOU HEAR ME OKAY?

579
00:24:40,320 --> 00:24:43,640
 >>  YOU SOUND GOOD, THANK YOU,

580
00:24:43,640 --> 00:24:45,040
 >> I THANK THE

581
00:24:45,040 --> 00:24:47,000
 ORGANIZERS FOR AN EXCELLENT

582
00:24:47,000 --> 00:24:50,000
 WORKSHOP AND A GREAT PRIVILEGE

583
00:24:50,000 --> 00:24:53,920
 TO SHARE TODAY EXPERIENCES WE

584
00:24:53,920 --> 00:25:02,080
 HAD WITH A LARGE PART OF

585
00:25:02,080 --> 00:25:05,760
 CONSORTIA FOR PRECISION

586
00:25:05,760 --> 00:25:08,960
 MEDICINE INVOLVED THE STUDY

587
00:25:08,960 --> 00:25:10,080
 AND TREATMENT.

588
00:25:10,080 --> 00:25:13,160
 SO THE STUDY WE TALK ABOUT

589
00:25:13,160 --> 00:25:23,440
 TODAY WAS FUNDID BY I GM F AS 

590
00:25:23,440 --> 00:25:26,840
 WELL AS OTHERS.

591
00:25:26,840 --> 00:25:30,160
 ANOTHER CONSORTIUM WAS FUNDED

592
00:25:30,160 --> 00:25:31,880
 BY IMS WHERE WE WERE TRYING TO

593
00:25:31,880 --> 00:25:33,400
 UNDERSTAND THE VARIATION OF

594
00:25:33,400 --> 00:25:36,440
 RESPONSE AMONG PEOPLE WHO ARE

595
00:25:36,440 --> 00:25:46,160
 DEPRESSED AND PEOPLE WITH 

596
00:25:46,160 --> 00:25:46,520
 DISORDERS.

597
00:25:46,520 --> 00:25:49,240
 AND TRANSLATING IDEAS FROM

598
00:25:49,240 --> 00:25:53,080
 CONSORTIUM TRYING TO 

599
00:25:53,080 --> 00:25:57,120
 UNDERSTAND AND THINK ABOUT

600
00:25:57,120 --> 00:26:03,280
 METABIOMICS IN A MOREPRECISE

601
00:26:03,280 --> 00:26:06,080
 WAY. 

602
00:26:06,080 --> 00:26:10,920
 ALSO NIH FUNDED THE STUDY YOU

603
00:26:10,920 --> 00:26:12,000
 SEE HERE.

604
00:26:12,000 --> 00:26:17,760
 BRIEFLY HOW WE VIEW THE WORD I

605
00:26:17,760 --> 00:26:20,200
 THINK IS THE FIRST THING AND

606
00:26:20,200 --> 00:26:25,920
 THAT IS WE ARE INFLUENCED BY

607
00:26:25,920 --> 00:26:27,960
 THE GENOME WHICH OF COURSE

608
00:26:27,960 --> 00:26:32,960
 TELLS US SOMETHING ABOUT

609
00:26:32,960 --> 00:26:33,680
 MORBIDITY, SUSCEPTIBILITY AND

610
00:26:33,680 --> 00:26:35,960
 INFORMS HOW WE RESPOND TO

611
00:26:35,960 --> 00:26:38,920
 MEDICATION -- IN SOME CASES,

612
00:26:38,920 --> 00:26:43,120
 NOT ALWAYS BUT THIS IS THE

613
00:26:43,120 --> 00:26:44,640
 INVOLVEMENT OF GENOMICS AND SO

614
00:26:44,640 --> 00:26:46,240
 THAT DATA IS IMPORTANT AND NOT

615
00:26:46,240 --> 00:26:49,680
 ONLY IS THAT IMPORTANT, WE ARE

616
00:26:49,680 --> 00:26:51,280
 REALIZING QUICKLY THAT THE

617
00:26:51,280 --> 00:26:54,000
 METHOD BY WHICH WE ARE EXPOSED

618
00:26:54,000 --> 00:26:58,320
 TO IT IS ALSO IMPORTANT AND

619
00:26:58,320 --> 00:27:04,600
 CAN BE USED FOR

620
00:27:04,600 --> 00:27:05,160
 SUSCEPTIBILITY.

621
00:27:05,160 --> 00:27:09,920
 AND ALSO GUT INFLUENCED BY THE

622
00:27:09,920 --> 00:27:10,840
 MICROBIOME.

623
00:27:10,840 --> 00:27:19,800
 THE GUT MICROBIOME AND STUDIES

624
00:27:19,800 --> 00:27:25,400
 EMERGING IS AT A CROSSROAD

625
00:27:25,400 --> 00:27:27,800
 WITH OUR DIET, OUR

626
00:27:27,800 --> 00:27:29,920
 ENVIRONMENT, SOCIAL NETWORKS,

627
00:27:29,920 --> 00:27:31,520
 ALL INTERCONNECTING THINGS

628
00:27:31,520 --> 00:27:33,560
 THAT DO DEFINE AT THE END WHO

629
00:27:33,560 --> 00:27:36,760
 WE ARE AS INDIVIDUALS AND WE

630
00:27:36,760 --> 00:27:39,880
 SHOW IN THE BACKGROUND THE

631
00:27:39,880 --> 00:27:40,800
 NETWORK THAT DESCRIBE

632
00:27:40,800 --> 00:27:42,200
 ULTIMATELY WHO WE ARE.

633
00:27:42,200 --> 00:27:47,040
 AND I WANT TO SCAMP GUY  SCAMP

634
00:27:47,040 --> 00:27:56,600
 GUY WHAT I MEAN BY THIS.

635
00:27:56,600 --> 00:27:57,000
 EXEMPLIFY.

636
00:27:57,000 --> 00:28:00,800
 SO WE LOOK AT THE METABOLIC

637
00:28:00,800 --> 00:28:01,920
 PATHWAYS AND PROCESSES

638
00:28:01,920 --> 00:28:02,800
 IMPLICATED IN HUMAN DISEASE

639
00:28:02,800 --> 00:28:10,160
 AND HOW THEY ARE INFLUENCED BY

640
00:28:10,160 --> 00:28:12,320
 THE MICROBIOME AND MEASURED IN

641
00:28:12,320 --> 00:28:16,200
 THE BLOOD OR OTHER TISSUES

642
00:28:16,200 --> 00:28:20,320
 REVEAL SUSCEPTIBILITY ON AN

643
00:28:20,320 --> 00:28:20,800
 INDIVIDUAL BASE.

644
00:28:20,800 --> 00:28:29,400
 WE HAVE LEARNED THROUGH

645
00:28:29,400 --> 00:28:36,440
 PARTNERSHIP WITH THE WEILL

646
00:28:36,440 --> 00:28:39,760
 CORNELL INSTITUTE, AND HOW WE 

647
00:28:39,760 --> 00:28:44,760
 LOOK AT ALL THESE AFFECTS IS

648
00:28:44,760 --> 00:28:49,480
 HIGHLY BASED ON OUR GENES.

649
00:28:49,480 --> 00:28:53,600
 SO THE STUDY FROM UNIVERSITY

650
00:28:53,600 --> 00:28:55,800
 OF CAMBRIDGE SHOWING HIGH

651
00:28:55,800 --> 00:28:59,760
 DENSITY FOR EACH, NOT ONLY CAN

652
00:28:59,760 --> 00:29:03,080
 THE AGAIN HOME IN IDENTIFY AN

653
00:29:03,080 --> 00:29:10,520
 IDENTITY BUT THE CHEMISTRY

654
00:29:10,520 --> 00:29:11,760
 SHOWS UNIQUE AMONG INDIVIDUALS

655
00:29:11,760 --> 00:29:13,160
 AND THIS CHANGES THE PARADIGM

656
00:29:13,160 --> 00:29:15,560
 OF HOW WE THINK ABOUT

657
00:29:15,560 --> 00:29:17,200
 PRECISION MEDICINE AND

658
00:29:17,200 --> 00:29:18,400
 PRECISION HEALTH.

659
00:29:18,400 --> 00:29:32,560
 NOT ONLY IS OUR METABOLISM

660
00:29:32,560 --> 00:29:35,880
 PLAYING A PART IN THE GENOME,

661
00:29:35,880 --> 00:29:39,160
 IT REALLY PUTS TOGETHER THE

662
00:29:39,160 --> 00:29:43,000
 INFLUENCES OF THE BACTERIA AND

663
00:29:43,000 --> 00:29:44,280
 METABOLITES MEASURED BY THE

664
00:29:44,280 --> 00:29:46,360
 PROFILE OF WHAT WE EAT.

665
00:29:46,360 --> 00:29:50,800
 SO THE GENOME AND MICROBIOME

666
00:29:50,800 --> 00:29:53,320
 BOTH GIVES US INFORMATION FOR

667
00:29:53,320 --> 00:29:57,000
 MEASUREMENT OF THE METABOLOME.

668
00:29:57,000 --> 00:30:02,720
 TO COMMENT ON THE SIN GEE, YOU

669
00:30:02,720 --> 00:30:08,360
 KNOW, WE KNOW THAT THE FIRST

670
00:30:08,360 --> 00:30:09,800
 METABOLITES WE INGEST, WHETHER

671
00:30:09,800 --> 00:30:12,320
 HIGH FIBER OR THE OTHER THINGS

672
00:30:12,320 --> 00:30:20,880
 WE TAKE IN, THROUGH OUR

673
00:30:20,880 --> 00:30:23,560
 GENETIC MAKEUP, AND BASED ON

674
00:30:23,560 --> 00:30:25,800
 WHAT WE INGEST, THERE IS A

675
00:30:25,800 --> 00:30:28,000
 WHOLE BUNCH OF ACTIVITY THAT

676
00:30:28,000 --> 00:30:34,760
 COMES FROM THIS AND THEY ALSO

677
00:30:34,760 --> 00:30:36,680
 PROVIDE FURTHER MATERIAL THAT

678
00:30:36,680 --> 00:30:43,000
 WE CONTINUE TO PRODUCE AS

679
00:30:43,000 --> 00:30:47,640
 HUMANS OF THE METABOLISM.

680
00:30:47,640 --> 00:30:50,760
 SO IT IS A TRUE PARTNERSHIP

681
00:30:50,760 --> 00:30:55,600
 BETWEEN BACTERIA AND THE HUMAN

682
00:30:55,600 --> 00:30:58,840
 AND GIVING US THE TARGETING

683
00:30:58,840 --> 00:30:59,320
 GUT MICROBIOME.

684
00:30:59,320 --> 00:31:06,400
 WE ARE TRYING TO UNDERSTAND

685
00:31:06,400 --> 00:31:11,080
 THE COMPLEXITY AND DIVERSITY

686
00:31:11,080 --> 00:31:15,800
 THE METABOLISM USES THE

687
00:31:15,800 --> 00:31:17,120
 BACTERIA, WE ARE ALSO SEE THAT

688
00:31:17,120 --> 00:31:19,280
 THE WORK CAN TEACH US ABOUT

689
00:31:19,280 --> 00:31:21,800
 THE BIOCHEMISTRY THAT IS

690
00:31:21,800 --> 00:31:27,200
 MODULATED BY THE MICROBIOME.

691
00:31:27,200 --> 00:31:34,080
 WE KNOW THERE IS A WHOLE LIST

692
00:31:34,080 --> 00:31:37,760
 OF BACTERIA IN THE MICROBIOME

693
00:31:37,760 --> 00:31:40,720
 THAT ARE EITHER PRODUCED BY

694
00:31:40,720 --> 00:31:42,320
 THE BACTERIA DIRECTLY OR

695
00:31:42,320 --> 00:31:43,600
 CORRELATED BY THE BACTERIA AND

696
00:31:43,600 --> 00:31:46,920
 I CAN GIVE YOU SPECIFIC

697
00:31:46,920 --> 00:31:48,560
 EXAMPLES.

698
00:31:48,560 --> 00:31:51,040
 FOR EXAMPLE, CHOLESTEROL, IT

699
00:31:51,040 --> 00:31:53,000
 IS METABOLIZED BY AN ENZYME

700
00:31:53,000 --> 00:31:56,280
 BUT THEN THERE IS A WHOLE

701
00:31:56,280 --> 00:31:59,840
 NUMBER OF ENZYMES THAT ARE

702
00:31:59,840 --> 00:32:03,480
 PRODUCED THAT COMPLETE THE

703
00:32:03,480 --> 00:32:05,000
 CHOLESTEROL THAT CAN IMPACT ON

704
00:32:05,000 --> 00:32:05,600
 HUMAN HEALTH.

705
00:32:05,600 --> 00:32:08,360
 SO I LOOK AT CHOLESTEROL AND

706
00:32:08,360 --> 00:32:09,720
 SAY THIS IS HUMAN AND THE REST

707
00:32:09,720 --> 00:32:15,680
 OF THIS IS THE BACTERIA, 

708
00:32:15,680 --> 00:32:17,160
 RIGHT?

709
00:32:17,160 --> 00:32:30,200
 SO THERE ARE OTHER FACTORS, 

710
00:32:30,200 --> 00:32:37,360
 CARBON, THE CHOLINE,.

711
00:32:37,360 --> 00:32:38,400
 [INDISCERNIBLE] MANY OF THESE

712
00:32:38,400 --> 00:32:39,360
 TURNED ON OR OFF.

713
00:32:39,360 --> 00:32:46,080
 SO IF WE ARE TALKING ABOUT

714
00:32:46,080 --> 00:32:47,800
 MICROBIOTICS, WE ARE TALKING

715
00:32:47,800 --> 00:32:50,960
 ABOUT THE END SILENCE AND

716
00:32:50,960 --> 00:32:52,320
 ACTIVITY THAT IT INFLUENCES

717
00:32:52,320 --> 00:32:59,040
 THAT SEEM TO BE THE RESULT OF

718
00:32:59,040 --> 00:32:59,920
 HUMAN HEALTH.

719
00:32:59,920 --> 00:33:03,600
 WE HAVE GROUPS WHO ARE DOING

720
00:33:03,600 --> 00:33:05,520
 THE SUBSCRIPTION TRYING TO

721
00:33:05,520 --> 00:33:07,480
 UNDERSTAND THE SYNERGY BETWEEN

722
00:33:07,480 --> 00:33:10,200
 THE HUMAN AND BACTERIA, TRYING

723
00:33:10,200 --> 00:33:19,440
 TO SEE HOW WE CAN MODULATE

724
00:33:19,440 --> 00:33:19,760
 THIS.

725
00:33:19,760 --> 00:33:29,800
 WE HAVE A PORTAL FOR BUILDING

726
00:33:29,800 --> 00:33:34,080
 ASPECTS OF BUILDING MICROBIAL

727
00:33:34,080 --> 00:33:36,680
 METABOLITES AND WHAT PROFESSOR

728
00:33:36,680 --> 00:33:38,880
 DAVID WISHART AND OTHERS HAVE

729
00:33:38,880 --> 00:33:40,360
 DONE IS DETERMINE THIS

730
00:33:40,360 --> 00:33:46,520
 BACTERIA WHERE WE CAN LOOK AT

731
00:33:46,520 --> 00:33:50,160
 THE ENVIRONMENT, THE DIET, AND

732
00:33:50,160 --> 00:33:57,160
 REVIEW THIS TO GIVE US MORE

733
00:33:57,160 --> 00:34:01,840
 RESOURCES, AND HOW THEY 

734
00:34:01,840 --> 00:34:06,720
 NETWORK WITH THE BACTERIA. 

735
00:34:06,720 --> 00:34:12,600
 WE KNOW THAT THE EXPOSOME DOES

736
00:34:12,600 --> 00:34:16,680
 INFLUENCE THE MICROBIOME AND

737
00:34:16,680 --> 00:34:17,080
 METABOLOME.

738
00:34:17,080 --> 00:34:19,840
 ALL ARE INTERCONNECTED AND ALL

739
00:34:19,840 --> 00:34:25,480
 INFLUENCE AND ARE MAJOR

740
00:34:25,480 --> 00:34:29,880
 DECISION MAKERS INCLUDING THE

741
00:34:29,880 --> 00:34:30,520
 METABOLOME.

742
00:34:30,520 --> 00:34:35,200
 I PULLED THIS STUDY LOOKING AT

743
00:34:35,200 --> 00:34:45,600
 THE VARIANCE OF BLOOD

744
00:34:45,600 --> 00:34:50,040
 METABOLOME, LOOKING AT THE

745
00:34:50,040 --> 00:34:56,640
 EXPOSOME OF BLOOD METABOLOME

746
00:34:56,640 --> 00:35:02,200
 AND ASK ABOUT THE RELATION OF 

747
00:35:02,200 --> 00:35:03,000
 COGNITION ASSOCIATED

748
00:35:03,000 --> 00:35:07,640
 METABOLITES WITH GUT, 

749
00:35:07,640 --> 00:35:09,760
 MEDICATION AND GENETICS, AND

750
00:35:09,760 --> 00:35:17,760
 CAN I CHANGE THE INFLUENCES OF

751
00:35:17,760 --> 00:35:20,240
 THE GUT MICROBIOME, AND WHAT

752
00:35:20,240 --> 00:35:24,800
 ARE THE INFLUENCES, WHICH

753
00:35:24,800 --> 00:35:26,560
 BACTERIA SCREENS AND WHICH ARE

754
00:35:26,560 --> 00:35:29,880
 IN THE MICROBIOME AND HOW THE

755
00:35:29,880 --> 00:35:32,360
 GENOME WILL INFLUENCE THE

756
00:35:32,360 --> 00:35:35,360
 INTERACTION OF GENOME GUT

757
00:35:35,360 --> 00:35:35,760
 MICROBIOME.

758
00:35:35,760 --> 00:35:42,320
 AND THE DRUGS WE ARE ON CAN

759
00:35:42,320 --> 00:35:44,400
 RESULT IN A VARIATION IN

760
00:35:44,400 --> 00:35:44,760
 QUALITY.

761
00:35:44,760 --> 00:35:47,680
 OR TO GIVE US THE OPPORTUNITY

762
00:35:47,680 --> 00:35:53,640
 TO TALK ABOUT THE QUALITY AND

763
00:35:53,640 --> 00:35:59,840
 INDOLES PRODUCED BY GUT

764
00:35:59,840 --> 00:36:00,200
 MICROBE.

765
00:36:00,200 --> 00:36:02,600
 WE KNOW THAT THEY CORRELATE

766
00:36:02,600 --> 00:36:08,600
 WITH ANXIETY AND DEPRESSION,

767
00:36:08,600 --> 00:36:13,920
 CERTAIN BACTERIA THAT IMPACTS 

768
00:36:13,920 --> 00:36:17,760
 THE BRAIN IN PROFOUND WAYS AND

769
00:36:17,760 --> 00:36:18,240
 WITH REGULARITY.

770
00:36:18,240 --> 00:36:22,920
 IF YOU LOOK AT THE HUMAN

771
00:36:22,920 --> 00:36:24,400
 BACTERIAL METALISM, IT IS

772
00:36:24,400 --> 00:36:27,160
 REGULATED BY GENES AND IN PART

773
00:36:27,160 --> 00:36:30,920
 IS ALSO PREDICTED BY THE

774
00:36:30,920 --> 00:36:37,440
 IMMUNITY BUT THE TRYPTOPHAN IN

775
00:36:37,440 --> 00:36:40,400
 THE GUT WILL PRODUCE

776
00:36:40,400 --> 00:36:45,120
 INDOTOXINS AND A THIRD OF

777
00:36:45,120 --> 00:36:54,520
 HUMANS CAN COMPLETE THIS BY 

778
00:36:54,520 --> 00:36:57,360
 MAKING BLOOD INDOXYL SULPHATE

779
00:36:57,360 --> 00:37:04,600
 LEVELS THAT CORAL LATER WITH 

780
00:37:04,600 --> 00:37:05,600
 ANXIETY AND DEPRESSION.

781
00:37:05,600 --> 00:37:07,440
 SO THIS COMES WITH A

782
00:37:07,440 --> 00:37:12,720
 PARTNERSHIP BETWEEN THE HUMAN

783
00:37:12,720 --> 00:37:16,360
 AND BACTERIA, THE HUMAN AND

784
00:37:16,360 --> 00:37:20,800
 THE ENDS SAME, THE CHANGES IN

785
00:37:20,800 --> 00:37:24,000
 THE BRAIN AND HERE ARE THE MRI

786
00:37:24,000 --> 00:37:27,520
 CHANGES IN A VERY SENSITIVE

787
00:37:27,520 --> 00:37:31,360
 AREA WHICH CORRELATES ARE 

788
00:37:31,360 --> 00:37:31,960
 ANXIETY AND DEPRESSION.

789
00:37:31,960 --> 00:37:34,480
 >> YOU HAVE THREE MINUTES.

790
00:37:34,480 --> 00:37:36,760
 >> OH, WE KNOW ALSO THESE

791
00:37:36,760 --> 00:37:38,320
 COMPOUNDS ARE IN THE BRAIN,

792
00:37:38,320 --> 00:37:38,600
 RIGHT?

793
00:37:38,600 --> 00:37:42,040
 SO IT GIVES US AN AVENUE TO

794
00:37:42,040 --> 00:37:44,320
 START TO THINK ABOUT

795
00:37:44,320 --> 00:37:46,400
 PROBIOTICS AND I HOPE THAT WE

796
00:37:46,400 --> 00:37:52,520
 CAN COMPLETE THE STORY HERE

797
00:37:52,520 --> 00:37:56,600
 AND SHOW THE COSMETIC APPROACH

798
00:37:56,600 --> 00:38:06,120
 OF HOW CAN WE IMPROVE THE

799
00:38:06,120 --> 00:38:06,880
 MICROBIOME.

800
00:38:06,880 --> 00:38:12,240
 SO THE EMERGING ROLE FOR GUT

801
00:38:12,240 --> 00:38:15,080
 MICROBIOME THROUGH BRAIN

802
00:38:15,080 --> 00:38:17,600
 IMAGING AND JUST A FEW WORDS

803
00:38:17,600 --> 00:38:23,040
 WHAT WE HAVE DONE AT NI GM S,

804
00:38:23,040 --> 00:38:25,800
 ONE SIZE DOES NOT FIT ALL.

805
00:38:25,800 --> 00:38:30,160
 THERE IS SYNERGY BETWEEN

806
00:38:30,160 --> 00:38:31,360
 GENETICS AND CONSORTIUM TO

807
00:38:31,360 --> 00:38:33,800
 HAVE NO RESPONSE OR COMPLETE

808
00:38:33,800 --> 00:38:38,360
 RESPONSE AND WITH SOME CLASSES

809
00:38:38,360 --> 00:38:44,280
 OF DRUGS, AFFECT THE GENOME OF

810
00:38:44,280 --> 00:38:45,000
 EACH INDIVIDUAL.

811
00:38:45,000 --> 00:38:47,320
 THIS LEADS TO BETTER

812
00:38:47,320 --> 00:38:49,200
 PREDICTION OF RESPONSE AND

813
00:38:49,200 --> 00:38:49,760
 VARIATION OF RESPONSE.

814
00:38:49,760 --> 00:38:53,240
 I DO NOT HAVE TIME TO GO

815
00:38:53,240 --> 00:39:00,720
 THROUGH ALL OF THIS BUT ONE 

816
00:39:00,720 --> 00:39:02,600
 STUDY OF ESCITALOPRAM

817
00:39:02,600 --> 00:39:03,520
 INVESTIGATION WITH THE MAYO

818
00:39:03,520 --> 00:39:04,920
 CLINIC, TO LOOK AT THE PEOPLE

819
00:39:04,920 --> 00:39:06,760
 WHO RESPOND AND DO NOT

820
00:39:06,760 --> 00:39:08,720
 RESPOND, NOW TO GET TO THE

821
00:39:08,720 --> 00:39:13,200
 ENZYME AND SEE THE REDUCED

822
00:39:13,200 --> 00:39:17,520
 FUNCTION OR DEGRADATION THAT 

823
00:39:17,520 --> 00:39:19,760
 IS NECESSARY TO SUPPORT AND

824
00:39:19,760 --> 00:39:23,200
 THE DRUGS THEY ARE TAKING, WE

825
00:39:23,200 --> 00:39:25,920
 SAW HOW IMPORTANT THEY ARE INY

826
00:39:25,920 --> 00:39:28,640
 FINING RESPONSE OR NO

827
00:39:28,640 --> 00:39:29,800
 RESPONSE.

828
00:39:29,800 --> 00:39:30,840
 THE BACTERIA THEREFORE DO PLAY

829
00:39:30,840 --> 00:39:34,720
 A ROLE IN HOW WE METABOLIZE

830
00:39:34,720 --> 00:39:35,880
 THE DRUG AND MUCH MORE.

831
00:39:35,880 --> 00:39:39,880
 SO NOW WE HAVE A RESPONSE, WE

832
00:39:39,880 --> 00:39:45,920
 CAN MAP THE GENETICS TO SEE

833
00:39:45,920 --> 00:39:48,640
 ETHNICITY AND HOW THAT

834
00:39:48,640 --> 00:39:50,920
 CONTRIBUTES TO VARIATION, WE

835
00:39:50,920 --> 00:39:53,280
 CAN LOOK AT WHAT IS THE

836
00:39:53,280 --> 00:39:55,480
 MECHANISM THAT IS DIFFERENT

837
00:39:55,480 --> 00:39:56,840
 BETWEEN THE RESPONDERS AND

838
00:39:56,840 --> 00:40:01,680
 OTHER RESPONDERS AND LOOK AT

839
00:40:01,680 --> 00:40:06,360
 MEN AND WOMEN WITH ASPIRIN AND

840
00:40:06,360 --> 00:40:07,600
 DETERMINE A RESPONSE.

841
00:40:07,600 --> 00:40:09,800
 THE RESULTS THAT WE FOUND IN

842
00:40:09,800 --> 00:40:16,720
 INDIA CAN BE APPLIED TO ANY

843
00:40:16,720 --> 00:40:17,000
 GROUP.

844
00:40:17,000 --> 00:40:18,800
 AND WHAT WE HAVE LEARNED IS

845
00:40:18,800 --> 00:40:23,480
 THE EXPOSURE OF THE MICROBIOME

846
00:40:23,480 --> 00:40:26,000
 AND CONTRIBUTION TO HUMAN

847
00:40:26,000 --> 00:40:27,040
 DISEASES, TO TEACH US

848
00:40:27,040 --> 00:40:29,680
 SOMETHING ABOUT THE RESPONSE,

849
00:40:29,680 --> 00:40:31,800
 THE VARIATION OF THE RESPONSE

850
00:40:31,800 --> 00:40:34,440
 AND IF YOU THINK OF

851
00:40:34,440 --> 00:40:36,880
 PROBIOTICS, HOW ARE WE GOING

852
00:40:36,880 --> 00:40:40,880
 TO CHANGE THE MICROBIOME, HOW 

853
00:40:40,880 --> 00:40:45,200
 WILL WE MARKET IT AND THE

854
00:40:45,200 --> 00:40:47,080
 QUANTITATIVE MEASURES THAT CAN

855
00:40:47,080 --> 00:40:55,760
 TELL US DID WE MODERATE THE

856
00:40:55,760 --> 00:40:58,800
 END RESULT FOR THE INDIVIDUAL.

857
00:40:58,800 --> 00:41:02,800
 >> THANK YOU, RIMA, THAT IS 

858
00:41:02,800 --> 00:41:04,920
 GREAT THOUGHT.

859
00:41:04,920 --> 00:41:10,640
 OUR NEXT SPEAKER WILL BE Dr.

860
00:41:10,640 --> 00:41:14,640
 MARK HAUPT, HIS TALK ENTITLED

861
00:41:14,640 --> 00:41:15,080
 IMPORTANCE OF INVESTIGATIONAL

862
00:41:15,080 --> 00:41:16,680
 PRODUCT MANUFACTURING FOR

863
00:41:16,680 --> 00:41:17,760
 PROBIOTIC INTERVENTION TRIALS.

864
00:41:17,760 --> 00:41:18,480
 TAKE IT AWAY, MARK.

865
00:41:18,480 --> 00:41:20,880
 THANK YOU FOR THIS OPPORTUNITY

866
00:41:20,880 --> 00:41:22,840
 TO JOIN YOU TODAY AND THANKS

867
00:41:22,840 --> 00:41:30,680
 TO THE ORGANIZERS WHO PUT THIS

868
00:41:30,680 --> 00:41:31,160
 TOGETHER.

869
00:41:31,160 --> 00:41:41,040
 I HAVE THE PRIVILEGE OF 

870
00:41:41,040 --> 00:41:44,600
 FILLING IN FOR Dr. STAHL TO

871
00:41:44,600 --> 00:41:46,880
 SHARE WITH YOU THE IMPORTANCE

872
00:41:46,880 --> 00:41:49,680
 OF VET TKPWAEUGSAL PRODUCT

873
00:41:49,680 --> 00:41:51,080
 MANUFACTURING FOR PROBIOTIC

874
00:41:51,080 --> 00:41:51,800
 INTERVENTION TRIALS.

875
00:41:51,800 --> 00:41:55,280
 I SPENT MY CAREER IN PHARMA

876
00:41:55,280 --> 00:42:00,760
 WORKING ON VARIOUS ELEMENTS 

877
00:42:00,760 --> 00:42:02,600
 INCLUDING PRECISION MEDICINE

878
00:42:02,600 --> 00:42:05,600
 THERAPYS AND APPROACHES AND 

879
00:42:05,600 --> 00:42:07,640
 HOW TO IDENTIFY THE RIGHT

880
00:42:07,640 --> 00:42:09,840
 PATIENTS TO THE RIGHT DRUGS,

881
00:42:09,840 --> 00:42:11,920
 THE RIGHT PRODUCT AND SO WHAT

882
00:42:11,920 --> 00:42:16,360
 I HOPE TO PROVIDE TODAY IS THE

883
00:42:16,360 --> 00:42:17,880
 LOOK INTO THE PROBIOTIC

884
00:42:17,880 --> 00:42:20,080
 PROCESS AND HOW TO IDENTIFY

885
00:42:20,080 --> 00:42:22,280
 THE STRAIN, HOW TO PRODUCE IT,

886
00:42:22,280 --> 00:42:22,880
 WHICH FORMULATION.

887
00:42:22,880 --> 00:42:25,280
 THERE ARE THINGS TO REALLY

888
00:42:25,280 --> 00:42:27,200
 CONSIDER WHEN PUTTING A TRIAL

889
00:42:27,200 --> 00:42:28,520
 TOGETHER TO INSURE YOU HAVE

890
00:42:28,520 --> 00:42:34,840
 THE GREATEST LIKELIHOOD OF

891
00:42:34,840 --> 00:42:35,200
 SUCCESS.

892
00:42:35,200 --> 00:42:38,360
 FOR DISCLOSURE, I AM AN 

893
00:42:38,360 --> 00:42:39,080
 EMPLOYEE OF IFF.

894
00:42:39,080 --> 00:42:43,560
 SO THE THINGS WE WILL WORK

895
00:42:43,560 --> 00:42:45,960
 THROUGH TODAY, WHAT ARE THE

896
00:42:45,960 --> 00:42:49,760
 OPPORTUNITY TO CONSIDER WHEN

897
00:42:49,760 --> 00:42:52,400
 CHOOSING WHICH PROBIOTIC FOR

898
00:42:52,400 --> 00:43:00,960
 HAVE VENGE, GETTING THE RIGHT 

899
00:43:00,960 --> 00:43:03,040
 FORMATS AND FORMULATIONS AND

900
00:43:03,040 --> 00:43:04,880
 WHAT ARE THE CHALLENGES AND

901
00:43:04,880 --> 00:43:08,680
 OPPORTUNITIES WITH THE FINAL

902
00:43:08,680 --> 00:43:10,000
 FORMAT SOLUTION, YOU WANT A

903
00:43:10,000 --> 00:43:11,680
 SOLUTION TO GET THE FINAL

904
00:43:11,680 --> 00:43:16,480
 PRODUCTS THROUGH AND THAT

905
00:43:16,480 --> 00:43:17,520
 INCLUDES SHIPPING, STORAGE,

906
00:43:17,520 --> 00:43:18,560
 ALL OF THOSE.

907
00:43:18,560 --> 00:43:22,480
 AND AGAIN, THIS IS NOT

908
00:43:22,480 --> 00:43:25,160
 DEFINITIVE IN GREAT DETAIL FOR

909
00:43:25,160 --> 00:43:26,160
 THE MANUFACTURING PROCESS BUT

910
00:43:26,160 --> 00:43:27,680
 TO INSURE WE HAVE THE RIGHT

911
00:43:27,680 --> 00:43:29,000
 SOLUTIONS FOR YOUR TRIAL, TO

912
00:43:29,000 --> 00:43:30,720
 ANSWER THE QUESTIONS YOU ARE

913
00:43:30,720 --> 00:43:31,280
 LOOKING TO ANSWER.

914
00:43:31,280 --> 00:43:35,400
 THIS IS A VERY HIGH LEVEL

915
00:43:35,400 --> 00:43:36,720
 OVERVIEW INTO PROBIOTICS

916
00:43:36,720 --> 00:43:38,280
 PROCESSING STEPS.

917
00:43:38,280 --> 00:43:44,320
 YOU HAVE THE PREPARATION, THE

918
00:43:44,320 --> 00:43:46,840
 NATURAL FILTERING PROCESS,

919
00:43:46,840 --> 00:43:47,760
 SEPARATING THE PRODUCT AND

920
00:43:47,760 --> 00:43:52,280
 THIS IS MAYBE A LITTLE

921
00:43:52,280 --> 00:43:53,400
 OVERSIMPLIFICATION OF THE

922
00:43:53,400 --> 00:43:55,680
 POINT, THIS IS NOT THE END

923
00:43:55,680 --> 00:43:57,840
 PRODUCT OR END DECISION OF

924
00:43:57,840 --> 00:44:01,720
 WHAT COMES OUT AS PROBIOTIC

925
00:44:01,720 --> 00:44:02,520
 FORMULATION.

926
00:44:02,520 --> 00:44:05,440
 MANY DECISIONS WE COULD MAKE

927
00:44:05,440 --> 00:44:07,480
 AFTER THIS TO INSURE WE HAVE

928
00:44:07,480 --> 00:44:08,320
 THE RIGHT ELEMENTS.

929
00:44:08,320 --> 00:44:14,120
 SO WHAT ARE THE STEPS FOR

930
00:44:14,120 --> 00:44:14,920
 DEVELOPING INVESTIGATIONAL

931
00:44:14,920 --> 00:44:15,480
 PRODUCTS?

932
00:44:15,480 --> 00:44:17,960
 FIRST OBVIOUSLY IS WHAT ARE

933
00:44:17,960 --> 00:44:18,840
 THE STRAINS.

934
00:44:18,840 --> 00:44:19,840
 SECOND, WHAT ARE THE CELL

935
00:44:19,840 --> 00:44:21,160
 COUNTS YOU ARE TRYING TO

936
00:44:21,160 --> 00:44:24,920
 STUDY, WHAT IS THE RANGE OF 

937
00:44:24,920 --> 00:44:36,360
 CELL COUNTS ACCEPTABLE, THE 

938
00:44:36,360 --> 00:44:36,880
 CONDITION THE STUDY.

939
00:44:36,880 --> 00:44:37,560
 AND THE VIABLE AND ADEQUATE

940
00:44:37,560 --> 00:44:38,240
 DOSES DELIVERED THROUGH THE

941
00:44:38,240 --> 00:44:39,200
 STUDY, THE DENSITY, INSURING

942
00:44:39,200 --> 00:44:42,520
 YOU HAVE HIGH QUALITY STRAINS

943
00:44:42,520 --> 00:44:44,480
 FREE OF CONTAMINATES AND ALL

944
00:44:44,480 --> 00:44:48,320
 OF THIS TOGETHER ADDRESSES THE

945
00:44:48,320 --> 00:44:49,120
 QUALITY AND SAFETY.

946
00:44:49,120 --> 00:44:52,680
 SO WHAT ARE SOME OF THE THINGS

947
00:44:52,680 --> 00:44:55,400
 NEEDED FOR THE CLINICAL TRIAL

948
00:44:55,400 --> 00:44:55,720
 DESIGN?

949
00:44:55,720 --> 00:44:57,280
 WHAT IS THE CORRECT STRAIN?

950
00:44:57,280 --> 00:45:01,480
 IS IT A SINGLE STRAIN OR

951
00:45:01,480 --> 00:45:03,680
 MULTIPLE STRAIN OF CONSORTIUM

952
00:45:03,680 --> 00:45:05,680
 YOU NEED TO DEMONSTRATE THE

953
00:45:05,680 --> 00:45:06,040
 INTENSITY?

954
00:45:06,040 --> 00:45:10,280
 WHAT IS THE DOSE?

955
00:45:10,280 --> 00:45:15,080
 THE LENGTH OF INTERVENTION AND

956
00:45:15,080 --> 00:45:20,080
 AGE OF PARTICIPANTS WITH THE 

957
00:45:20,080 --> 00:45:21,400
 MATERIAL WE PROVIDING.

958
00:45:21,400 --> 00:45:26,440
 THE AGE OF PARTICIPANTS, DO

959
00:45:26,440 --> 00:45:29,560
 THEY REPRESENT ADULTS AND THE

960
00:45:29,560 --> 00:45:32,480
 CHANGES IN THE LIVER TO THE

961
00:45:32,480 --> 00:45:38,880
 PROBIOTIC, THE ANALYSIS OF

962
00:45:38,880 --> 00:45:41,480
 METHODS TO INCLUDE DIVERSITY

963
00:45:41,480 --> 00:45:42,600
 AND THE POPULATIONS

964
00:45:42,600 --> 00:45:44,040
 DIFFERENCES, WHAT ARE THE

965
00:45:44,040 --> 00:45:46,040
 CRITERIA YOU LOOK AT IN THE

966
00:45:46,040 --> 00:45:49,280
 POPULATION TO EVALUATE AND 

967
00:45:49,280 --> 00:45:51,240
 THIS MAY ULTIMATELY INFORM THE

968
00:45:51,240 --> 00:45:53,960
 STRAIN YOU BACTERIA USED IN

969
00:45:53,960 --> 00:45:54,680
 THE STUDIES.

970
00:45:54,680 --> 00:45:56,680
 THE OTHER THING TO CONSIDER IS

971
00:45:56,680 --> 00:45:58,280
 THE CHARACTERISTIC OF WHERE

972
00:45:58,280 --> 00:46:00,880
 THIS STUDY WILL BE CONDUCTED

973
00:46:00,880 --> 00:46:03,480
 BECAUSE THIS INFORMS WHAT IS

974
00:46:03,480 --> 00:46:04,800
 PROVIDED, THE SUPPLY CHAIN FED

975
00:46:04,800 --> 00:46:07,400
 TO THE LIVER OF OF PROBIOTIC,

976
00:46:07,400 --> 00:46:22,520
 TO MAKE SURE IT IS SAFE, TO

977
00:46:22,520 --> 00:46:27,280
 MAKE SURE THE THEY ARE STORY

978
00:46:27,280 --> 00:46:28,800
 AND STORAGE CONDITIONS ARE

979
00:46:28,800 --> 00:46:35,360
 SATS IF A ACCIDENT TREE AT THE

980
00:46:35,360 --> 00:46:36,680
 SITE.

981
00:46:36,680 --> 00:46:37,920
 LEVERAGING HISTORICAL TRIALS

982
00:46:37,920 --> 00:46:40,120
 WITH THE DESIGN DATA TO INFORM

983
00:46:40,120 --> 00:46:42,720
 NEW TRIAL DESIGNS CAN BE

984
00:46:42,720 --> 00:46:45,680
 INFORMATIVE BUT DIRECT

985
00:46:45,680 --> 00:46:46,440
 TRANSMISSION IS INDIVIDUAL.

986
00:46:46,440 --> 00:46:48,480
 SO WHAT ARE THE KEY QUESTIONS

987
00:46:48,480 --> 00:46:51,320
 WE EXPLORE PRIOR TO ENGAGING

988
00:46:51,320 --> 00:46:53,480
 WITH A SUPPLIER FOR A

989
00:46:53,480 --> 00:46:54,760
 PROBIOTIC SOLUTION?

990
00:46:54,760 --> 00:46:56,480
 FIRST OF ALL, WHAT STRAINS

991
00:46:56,480 --> 00:47:00,360
 WILL BE STUDIED AND WHAT TOES?

992
00:47:00,360 --> 00:47:00,680
 DOSE?

993
00:47:00,680 --> 00:47:05,520
 AND WE WILL GET INTO THAT.

994
00:47:05,520 --> 00:47:06,480
 THERE ARE DIFFERENT STRAINS

995
00:47:06,480 --> 00:47:09,360
 THAT HAVE THE POTENTIAL FOR

996
00:47:09,360 --> 00:47:11,440
 EFFICACY AT DIFFERENT DOSES.

997
00:47:11,440 --> 00:47:15,960
 IS IT GOING TO BE STUDIED AT

998
00:47:15,960 --> 00:47:17,360
 1B, 5B?

999
00:47:17,360 --> 00:47:18,160
 WOULD MULTIPLE STRAINS

1000
00:47:18,160 --> 00:47:20,360
 INCREASE THE CHANCE FOR

1001
00:47:20,360 --> 00:47:21,440
 SUCCESS?

1002
00:47:21,440 --> 00:47:22,400
 WHAT ABOUT PREBIOTICS?

1003
00:47:22,400 --> 00:47:25,640
 SO IF YOU ARE STUDYING

1004
00:47:25,640 --> 00:47:29,680
 MULTIPLE STRAINS, YOU WILL

1005
00:47:29,680 --> 00:47:30,880
 HAVE DIFFERENT OUTCOMES.

1006
00:47:30,880 --> 00:47:32,840
 HOW WILL THE PRODUCT DELIVER?

1007
00:47:32,840 --> 00:47:41,000
 AND IT IS NOT JUST TO THE 

1008
00:47:41,000 --> 00:47:42,760
 INDIVIDUAL BUT MAKING CERTAIN

1009
00:47:42,760 --> 00:47:46,280
 YOU HAVE THE RIGHT FORMAT, A

1010
00:47:46,280 --> 00:47:48,600
 WAY TO STORE AT THE DELIVERY

1011
00:47:48,600 --> 00:47:51,360
 SYSTEM TO MAKE SURE YOU HAVE

1012
00:47:51,360 --> 00:47:53,280
 PRODUCTIVITY AND STABILITY

1013
00:47:53,280 --> 00:47:55,680
 REQUIRED TO DELIVER THE

1014
00:47:55,680 --> 00:47:58,600
 PRODUCT. 

1015
00:47:58,600 --> 00:48:00,000
 SO WHEN SPEAKING ABOUT WHICH

1016
00:48:00,000 --> 00:48:01,080
 STRAIN TO CHOOSE WHICH HAS

1017
00:48:01,080 --> 00:48:03,680
 BEEN BROUGHT UP A NUMBER OF

1018
00:48:03,680 --> 00:48:05,960
 TIMES, WE LOOK AT THE FUNCTION

1019
00:48:05,960 --> 00:48:07,120
 OF THE VARIOUS STRAINS AND

1020
00:48:07,120 --> 00:48:12,320
 CERTAINLY THIS IS A VERY HIGH 

1021
00:48:12,320 --> 00:48:21,920
 LEVEL OVERVIEW OF THE STRAIN

1022
00:48:21,920 --> 00:48:22,280
 SELECTION.

1023
00:48:22,280 --> 00:48:28,400
 SO AS YOU CAN SEE HERE, THE

1024
00:48:28,400 --> 00:48:32,360
 VARIOUS STRAINS ARE OF

1025
00:48:32,360 --> 00:48:34,760
 INTEREST, HEALTH CONDITIONS

1026
00:48:34,760 --> 00:48:37,680
 CAN INFORM AREAS, DELIVERED

1027
00:48:37,680 --> 00:48:38,840
 WITH FIBER DEPENDING ON THE

1028
00:48:38,840 --> 00:48:41,680
 STRAIN BUT THE ADDITIONAL

1029
00:48:41,680 --> 00:48:44,480
 NUANCES NEED TO BE COVERED IN

1030
00:48:44,480 --> 00:48:52,000
 THE VARIOUS POPULATIONS TO PUT

1031
00:48:52,000 --> 00:48:54,080
 TOGETHER AN OPPORTUNITY SO

1032
00:48:54,080 --> 00:48:55,480
 LOOKING AT WHAT DATA ARE

1033
00:48:55,480 --> 00:48:57,320
 NEEDED TO HELP YOU DESIGN

1034
00:48:57,320 --> 00:48:59,320
 THIS.

1035
00:48:59,320 --> 00:49:04,240
 WHEN WE TALK ABOUT EXTREMES,

1036
00:49:04,240 --> 00:49:06,840
 WE THINK ABOUT PROTOCOL, WHAT

1037
00:49:06,840 --> 00:49:10,840
 DOES IT TAKE TO BE A

1038
00:49:10,840 --> 00:49:13,480
 PROBIOTIC, TO INSURE THE

1039
00:49:13,480 --> 00:49:17,280
 STABILITY, MAKE SURE IT IS

1040
00:49:17,280 --> 00:49:26,600
 SAFE. 

1041
00:49:26,600 --> 00:49:27,560
 THE OTHER ENVIRONMENTAL

1042
00:49:27,560 --> 00:49:28,720
 CONDITIONS MAKING SURE THERE

1043
00:49:28,720 --> 00:49:34,680
 ARE NO FOREIGN ELEMENTS IN IT,

1044
00:49:34,680 --> 00:49:36,280
 INSURING APPROPRIATE QUALITY,

1045
00:49:36,280 --> 00:49:39,160
 MAKING SURE THE STRAINS ARE

1046
00:49:39,160 --> 00:49:40,560
 IDENTIFIED AND PUT TOGETHER,

1047
00:49:40,560 --> 00:49:44,800
 YOU KNOW WHAT YOU ARE PUTTING

1048
00:49:44,800 --> 00:49:46,400
 INTO YOUR PATIENT.

1049
00:49:46,400 --> 00:49:48,000
 SURVIVABILITY, TO INSURE THAT

1050
00:49:48,000 --> 00:49:54,600
 YOU HAVE LIVE PROBIOTICS AND 

1051
00:49:54,600 --> 00:49:56,920
 UNDERSTANDING THE CLINICAL

1052
00:49:56,920 --> 00:49:58,080
 SURVIVABILITY.

1053
00:49:58,080 --> 00:50:01,760
 THE KWROEFRPBLG HYPOTHESIS FOR

1054
00:50:01,760 --> 00:50:03,280
 END OF SHELF-LIFE TARGET, THIS

1055
00:50:03,280 --> 00:50:09,680
 IS AN EXAMINER SHOWING AS WE 

1056
00:50:09,680 --> 00:50:12,040
 PRODUCE A PROBIOTIC, WE START

1057
00:50:12,040 --> 00:50:14,200
 THE UNIT AT THE TIME OF

1058
00:50:14,200 --> 00:50:19,720
 MANUFACTURING ON THE

1059
00:50:19,720 --> 00:50:21,480
 PRODUCTION LINE, AND WILL

1060
00:50:21,480 --> 00:50:24,520
 REDUCE OVER TIME WITH

1061
00:50:24,520 --> 00:50:25,240
 INVESTIGATIONAL PRODUCT

1062
00:50:25,240 --> 00:50:27,760
 RELEASE AND THAT TRANSLATES TO

1063
00:50:27,760 --> 00:50:29,680
 END OF SHELF-LIFE TARGETED

1064
00:50:29,680 --> 00:50:32,000
 POTENCY SO WE NEED TO INSURE

1065
00:50:32,000 --> 00:50:42,480
 THAT THE SPECIFIC ELEMENTS ARE

1066
00:50:42,480 --> 00:50:44,480
 INTENDED FOR SHELF-LIFE.

1067
00:50:44,480 --> 00:50:48,520
 AND ARE THE INGREDIENTS 

1068
00:50:48,520 --> 00:50:49,760
 SUITABLE FOR PROBIOTIC

1069
00:50:49,760 --> 00:50:50,240
 SURVIVAL?

1070
00:50:50,240 --> 00:50:53,720
 AND IF NOT, WE NEED TO EXCLUDE

1071
00:50:53,720 --> 00:50:54,480
 THOSE PRODUCTS.

1072
00:50:54,480 --> 00:51:01,800
 THIS IS AN EXAMPLE OF BI-26

1073
00:51:01,800 --> 00:51:05,680
 STABILITY IN INFANTS FORMULA

1074
00:51:05,680 --> 00:51:06,880
 STORED IN DIFFERENT

1075
00:51:06,880 --> 00:51:07,280
 CONDITIONS.

1076
00:51:07,280 --> 00:51:11,280
 SO IF YOU LOOK HERE AT THE

1077
00:51:11,280 --> 00:51:15,680
 LABEL CLAIM OF 18 PER WILL

1078
00:51:15,680 --> 00:51:17,240
 .3 GRAMS SERVING, THIS IS

1079
00:51:17,240 --> 00:51:21,120
 GETTING INTO THE FORMAT OF THE

1080
00:51:21,120 --> 00:51:24,080
 POWDER PROVIDED AND PACKAGING

1081
00:51:24,080 --> 00:51:25,800
 IN DIFFERENT CLIMB ZONES BUT

1082
00:51:25,800 --> 00:51:36,880
 WHAT YOU SEE HERE IS THE TIME

1083
00:51:36,880 --> 00:51:39,320
 THE FORMULA WAS PRODUCED UNDER

1084
00:51:39,320 --> 00:51:43,280
 DIFFERENT CONDITIONS, YOU CAN

1085
00:51:43,280 --> 00:51:47,880
 SEE THE REDUCED EFFICACY.

1086
00:51:47,880 --> 00:51:49,680
 SO THIS IS AN EXAMPLE, A

1087
00:51:49,680 --> 00:51:54,360
 PICTURE OF ONE OF OUR

1088
00:51:54,360 --> 00:51:54,960
 INVESTIGATIONAL PRODUCT

1089
00:51:54,960 --> 00:51:55,960
 SUITES, AND KNEES ARE

1090
00:51:55,960 --> 00:51:58,960
 QUESTIONS TO BE ASKED OF YOUR

1091
00:51:58,960 --> 00:52:02,680
 SUPPLIER, WHAT DOES THE

1092
00:52:02,680 --> 00:52:03,960
 FORMULATION LOOK LIKE, WHAT

1093
00:52:03,960 --> 00:52:06,160
 ARE THE MEASURES TAKEN TO

1094
00:52:06,160 --> 00:52:09,280
 INSURE COMPLIANCE, WHAT ARE

1095
00:52:09,280 --> 00:52:10,120
 THE FORMATTING IMPLICATIONS

1096
00:52:10,120 --> 00:52:17,160
 DESIGNED AND HOW CAN YOU 

1097
00:52:17,160 --> 00:52:17,880
 FORMULATE, THAT?

1098
00:52:17,880 --> 00:52:20,360
 THIS IS AN EXAMPLE OF

1099
00:52:20,360 --> 00:52:22,160
 INVESTIGATIONAL PRODUCT

1100
00:52:22,160 --> 00:52:23,280
 TESTING AND LABELING, THE

1101
00:52:23,280 --> 00:52:24,520
 LABELING THAT GOES ON THE

1102
00:52:24,520 --> 00:52:26,120
 PRODUCT AND THE POINT TO KEEP

1103
00:52:26,120 --> 00:52:29,840
 IN MIND HERE AND THIS IS

1104
00:52:29,840 --> 00:52:31,720
 CRITICAL, THE CAPSULES ARE

1105
00:52:31,720 --> 00:52:34,000
 VERY GOOD FOR STABILITY

1106
00:52:34,000 --> 00:52:35,600
 ALTHOUGH IT MAY INTRODUCE

1107
00:52:35,600 --> 00:52:38,800
 CHALLENGES IN SOME

1108
00:52:38,800 --> 00:52:39,200
 POPULATIONS.

1109
00:52:39,200 --> 00:52:41,000
 SACHETS ARE THE EASIEST FOR

1110
00:52:41,000 --> 00:52:46,720
 STABILITY BUT NEED VERY

1111
00:52:46,720 --> 00:52:49,040
 SPECIFIC INSTRUCTIONS ON HOW

1112
00:52:49,040 --> 00:52:50,360
 TO TAKE THEM.

1113
00:52:50,360 --> 00:52:53,160
 FOOD FORMATS CAN BE DIFFICULT

1114
00:52:53,160 --> 00:52:55,080
 FOR STABILITY DUE TO SHELF

1115
00:52:55,080 --> 00:53:00,960
 LIVELY AND READY-TO-DRINK

1116
00:53:00,960 --> 00:53:02,040
 BEVERAGES HAVE OTHER

1117
00:53:02,040 --> 00:53:03,040
 CHALLENGES WITH SHIPPING AND

1118
00:53:03,040 --> 00:53:03,320
 SO ON.

1119
00:53:03,320 --> 00:53:06,800
 >> YOU HAVE JUST A FEW MINUTES

1120
00:53:06,800 --> 00:53:07,280
 LEFT.

1121
00:53:07,280 --> 00:53:08,280
 >> NO PROBLEM, THANK YOU.

1122
00:53:08,280 --> 00:53:12,800
 THIS IS APP EXAMPLE OF A

1123
00:53:12,800 --> 00:53:14,440
 FORMAT TO BE DEVELOPED TO MEET

1124
00:53:14,440 --> 00:53:24,600
 THE NEEDS OF A STUDY, THE 

1125
00:53:24,600 --> 00:53:28,160
 BI-26 IS SPRINKLED AS A METHOD

1126
00:53:28,160 --> 00:53:30,360
 OF DELIVERY TO HELP HEALTHY

1127
00:53:30,360 --> 00:53:32,320
 IMMUNE DEVELOPMENT IN INFANTS

1128
00:53:32,320 --> 00:53:33,240
 AND CHILDREN.

1129
00:53:33,240 --> 00:53:36,320
 SO REALLY WHEN IT ALL COMES

1130
00:53:36,320 --> 00:53:41,920
 TOGETHER, PUTTING TOGETHER

1131
00:53:41,920 --> 00:53:44,800
 PROBIOTIC SCIENCE, NEEDS GOOD

1132
00:53:44,800 --> 00:53:46,440
 PARTNERSHIP AND DELIVERING

1133
00:53:46,440 --> 00:53:48,960
 WITH THE EXPERTISE OF

1134
00:53:48,960 --> 00:53:55,160
 MANUFACTURERS TO INSURE WE 

1135
00:53:55,160 --> 00:53:57,960
 HAVE THIS INTENDED OUTCOME

1136
00:53:57,960 --> 00:53:58,920
 WITH THE POPULATION.

1137
00:53:58,920 --> 00:54:01,920
 AND IT REALLY TAKES THE

1138
00:54:01,920 --> 00:54:02,520
 PARTNERSHIP DISCUSSION

1139
00:54:02,520 --> 00:54:08,640
 SPECIFICALLY TO TALK ABOUT THE

1140
00:54:08,640 --> 00:54:10,520
 DETAILS AND SO I WILL END WITH

1141
00:54:10,520 --> 00:54:16,680
 THAT AND IF YOU HAVE QUESTIONS

1142
00:54:16,680 --> 00:54:18,080
 FURTHER ABOUT THIS, I WILL BE

1143
00:54:18,080 --> 00:54:20,720
 HAPPY TO TALK TO YOU AS WELL

1144
00:54:20,720 --> 00:54:23,040
 AND APPRECIATE YOUR

1145
00:54:23,040 --> 00:54:23,480
 PARTICIPATION.

1146
00:54:23,480 --> 00:54:25,080
 >> GREAT, MARK, THANKS AGAIN.

1147
00:54:25,080 --> 00:54:27,480
 WE WILL TURN THIS OVER TO

1148
00:54:27,480 --> 00:54:28,720
 KATHERINE FOR OUR FIRST BREAK

1149
00:54:28,720 --> 00:54:29,840
 OF THE DAY.

1150
00:54:29,840 --> 00:54:33,320
 >> WE ARE INDEED, THANK YOU,

1151
00:54:33,320 --> 00:54:33,800
 Dr. LUNSFORD.

1152
00:54:33,800 --> 00:54:36,600
 WE ARE GOING TO TAKE A

1153
00:54:36,600 --> 00:54:42,720
 5-MINUTE BREAK, EVERYBODY,

1154
00:54:42,720 --> 00:54:44,040
 DRINK WATER, STRETCH, WALK

1155
00:54:44,040 --> 00:54:46,760
 AROUND, WILL COME BACK AT

1156
00:54:46,760 --> 00:54:48,280
 11:45 EASTERN AND A REMINDER

1157
00:54:48,280 --> 00:54:49,880
 TO PARTICIPANTS TO MUTE YOUR

1158
00:54:49,880 --> 00:54:52,600
 AUDIO AND STOP SHARING YOUR

1159
00:54:52,600 --> 00:54:55,360
 VIDEO AND WE WILL ALL BE BACK

1160
00:54:55,360 --> 00:54:56,440
 HERE IN FIVE MINUTES.

1161
00:54:56,440 --> 00:54:59,640
 AND I AM GOING TO BE SHARING A

1162
00:54:59,640 --> 00:55:00,720
 BRIEF BREAK SLIDE WHILE THEY

1163
00:55:00,720 --> 00:55:01,520
 ARE AWAY.

1164
00:55:01,520 --> 00:55:02,120
 THANK YOU EVERYONE, SEE YOU IN

1165
00:55:02,120 --> 00:55:04,560
 FIVE MINUTES. 

1166
00:55:04,560 --> 00:55:06,760
 >> OUR NEXT SPEAKER EVERYONE

1167
00:55:06,760 --> 00:55:09,520
 IS SUSAN LYNCH FROM

1168
00:55:09,520 --> 00:55:12,360
 THE UNIVERSITY OF

1169
00:55:12,360 --> 00:55:14,040
 CALIFORNIA-SAN FRANCISCO AND

1170
00:55:14,040 --> 00:55:16,280
 HER TALK IS PRY BIOTIC

1171
00:55:16,280 --> 00:55:17,800
 CLINICAL TRIALS, OPPORTUNITY

1172
00:55:17,800 --> 00:55:19,840
 TO UNDERSTAND HUMAN

1173
00:55:19,840 --> 00:55:20,280
 MICROBIOLOGY.

1174
00:55:20,280 --> 00:55:21,560
 >> THANK YOU SO MUCH AND

1175
00:55:21,560 --> 00:55:23,800
 THANKS TO THE ORGANIZERS FOR

1176
00:55:23,800 --> 00:55:25,280
 THE INVITATION TO BE HERE

1177
00:55:25,280 --> 00:55:25,720
 TODAY.

1178
00:55:25,720 --> 00:55:28,720
 BEFORE I START BY WAY OF

1179
00:55:28,720 --> 00:55:31,920
 DISCLOSURE TO SAY I AM

1180
00:55:31,920 --> 00:55:34,880
 COFOUNDERRER AND SERVE AS

1181
00:55:34,880 --> 00:55:40,000
 BOARD OF DIRECTORS, CULT STAND

1182
00:55:40,000 --> 00:55:40,960
 FOR SIOLTA THERAPEUTICS AND

1183
00:55:40,960 --> 00:55:43,040
 WILL NOT BE TALKING ABOUT ANY

1184
00:55:43,040 --> 00:55:45,120
 WORK GOING ON IN THOSE REALMS

1185
00:55:45,120 --> 00:55:45,440
 TODAY.

1186
00:55:45,440 --> 00:55:49,880
 SO HOW WE AS A GROUP TRY TO

1187
00:55:49,880 --> 00:55:51,720
 PRAOEUFRB MICROBIOME RESEARCH

1188
00:55:51,720 --> 00:55:53,200
 IS REALLY MOVING AT FULL SCALE

1189
00:55:53,200 --> 00:55:58,560
 AND I THINK OF IT AS

1190
00:55:58,560 --> 00:56:03,720
 MULTIDATA, HOW MANY 

1191
00:56:03,720 --> 00:56:04,880
 POPULATIONS, UNDERSTANDING

1192
00:56:04,880 --> 00:56:06,880
 MICROBIOTA, MICROBIAL SPECIES

1193
00:56:06,880 --> 00:56:11,400
 AND STRAINS AND THE CELLULAR

1194
00:56:11,400 --> 00:56:13,920
 AND MOLECULAR AND HOW THAT

1195
00:56:13,920 --> 00:56:16,520
 APPLIES TO CLINICAL OUTCOMES.

1196
00:56:16,520 --> 00:56:20,480
 SO THIS REALLY SHOWS A

1197
00:56:20,480 --> 00:56:21,440
 MULTIAPPROACH TO THE STUDIES

1198
00:56:21,440 --> 00:56:23,400
 AND MOVING FROM HUMAN

1199
00:56:23,400 --> 00:56:24,560
 POPULATIONS AND FILLING THESE

1200
00:56:24,560 --> 00:56:26,960
 GAPS IN OUR KNOWLEDGE TO

1201
00:56:26,960 --> 00:56:28,040
 UNDERSTAND WHO PROBIOTICS WORK

1202
00:56:28,040 --> 00:56:30,440
 FOR AND HOW THEY MAY OPERATE

1203
00:56:30,440 --> 00:56:32,280
 WITHIN THE COMPLEX OF THE GUT

1204
00:56:32,280 --> 00:56:32,680
 MICROBIOME.

1205
00:56:32,680 --> 00:56:34,800
 SO I WANT TO SHARE WITH YOU A

1206
00:56:34,800 --> 00:56:36,120
 STUDY THAT WE PERFORMED A

1207
00:56:36,120 --> 00:56:41,320
 NUMBER OF YEARS AGO IN

1208
00:56:41,320 --> 00:56:44,240
 COLLABORATION WITH U.S. FF, A

1209
00:56:44,240 --> 00:56:51,600
 CLINICAL TRIAL OF INFANT

1210
00:56:51,600 --> 00:56:53,760
 PROBIOTIC SUPPLEMENTATION AND

1211
00:56:53,760 --> 00:56:57,320
 FOR HIGH RISK FOR ASTHMA

1212
00:56:57,320 --> 00:56:58,480
 INFANTS, DEFINED BASED ON THEY

1213
00:56:58,480 --> 00:57:06,160
 HAD AT LEAST ONE PARENT WITH

1214
00:57:06,160 --> 00:57:07,200
 DIAGNOSED ASTHMA.

1215
00:57:07,200 --> 00:57:11,360
 THE BABIES WERE SIX TO TEN

1216
00:57:11,360 --> 00:57:13,800
 MONTHS FOLLOWED BY A WASHOUT

1217
00:57:13,800 --> 00:57:18,040
 PERIOD OF 12 MONTHS AND THEN

1218
00:57:18,040 --> 00:57:22,440
 SEEN AT 3 YEARS OF AGE AND A

1219
00:57:22,440 --> 00:57:24,480
 BIT OF SPOILER ALERT, THERE

1220
00:57:24,480 --> 00:57:25,440
 WAS NO SIGNIFICANT DIFFERENCE

1221
00:57:25,440 --> 00:57:26,920
 BETWEEN THE PREVIOUSLY

1222
00:57:26,920 --> 00:57:28,760
 SUPPLEMENTED AND THE PLACEBO

1223
00:57:28,760 --> 00:57:30,720
 GROUP IN THIS STUDY BUT

1224
00:57:30,720 --> 00:57:31,640
 SUGGESTS THAT WE COULD

1225
00:57:31,640 --> 00:57:32,600
 ACTUALLY UNDERSTAND A LITTLE

1226
00:57:32,600 --> 00:57:39,640
 BIT MORE ABOUT HOW PROBIOTIC

1227
00:57:39,640 --> 00:57:41,240
 SUPPLEMENTATION INFLUENCES THE

1228
00:57:41,240 --> 00:57:42,520
 GUT MICROBIOME AND WHETHER

1229
00:57:42,520 --> 00:57:43,600
 THERE ARE DIFFERENCES TO BE

1230
00:57:43,600 --> 00:57:45,760
 LEARNED FROM THIS TRIAL.

1231
00:57:45,760 --> 00:57:49,760
 IN PARALLEL TO HIGH RISK

1232
00:57:49,760 --> 00:57:52,600
 INFANTS, MICHAEL ALSO HAD A

1233
00:57:52,600 --> 00:58:01,400
 COHORT OF HC INFANTS AND

1234
00:58:01,400 --> 00:58:05,040
 PURELY ON SUPPLEMENTATION HAD 

1235
00:58:05,040 --> 00:58:07,320
 THE FORESIGHT TO COLLECT

1236
00:58:07,320 --> 00:58:12,440
 SAMPLES FROM THE INFANTS AND

1237
00:58:12,440 --> 00:58:16,600
 THIS ALLOWED US TO USE MRNA

1238
00:58:16,600 --> 00:58:20,400
 SEQUENCING AND TARGETED ON THE

1239
00:58:20,400 --> 00:58:21,200
 LG AND HC ASPECT.

1240
00:58:21,200 --> 00:58:22,800
 AND THE FIRST THING OBVIOUS TO

1241
00:58:22,800 --> 00:58:25,120
 US WAS THAT COMPARED TO

1242
00:58:25,120 --> 00:58:27,800
 INFANTS SHOWN HERE IN GREEN OR

1243
00:58:27,800 --> 00:58:30,280
 THE HEALTHY CONTROL ARM,

1244
00:58:30,280 --> 00:58:33,600
 BABIES BORN TO HIGH RISK FOR

1245
00:58:33,600 --> 00:58:36,040
 ALLERGY AND ASTHMA BABIES

1246
00:58:36,040 --> 00:58:37,800
 DEMONSTRATED A SIGNIFICANTLY

1247
00:58:37,800 --> 00:58:41,640
 DIFFERENT TRAJECTORY OF GUT

1248
00:58:41,640 --> 00:58:42,400
 MICROBIOMES, SIGNIFICANTLY

1249
00:58:42,400 --> 00:58:44,640
 LOWER THAN THAT OF THE HEALTHY

1250
00:58:44,640 --> 00:58:45,400
 CONTROLLED SUBJECTS.

1251
00:58:45,400 --> 00:58:51,280
 BUT THOSE HIGH RISK INFANTS

1252
00:58:51,280 --> 00:58:52,760
 WHO RECEIVED THE SUPPLEMENTS

1253
00:58:52,760 --> 00:58:54,480
 FOR THE FIRST SIX MONTHS OF

1254
00:58:54,480 --> 00:58:58,040
 LIFE NO LONGER DEMONSTRATED

1255
00:58:58,040 --> 00:58:59,600
 THE SIGNIFICANT DIFFERENCE IN

1256
00:58:59,600 --> 00:59:00,880
 SLOPE IN ACCUMULATION OF

1257
00:59:00,880 --> 00:59:03,320
 DIVERSITY BUT AS YOU CAN SEE,

1258
00:59:03,320 --> 00:59:05,440
 THEY STILL HAVE DEFICIENCIES

1259
00:59:05,440 --> 00:59:07,640
 IN THE MICROBIOME AND LARGELY

1260
00:59:07,640 --> 00:59:09,560
 DUE TO A HE COULD TPHR*EGS

1261
00:59:09,560 --> 00:59:12,040
 LEGS OF RICHNESS, ACCUMULATION

1262
00:59:12,040 --> 00:59:14,000
 OF DIFFERENT TYPES OF

1263
00:59:14,000 --> 00:59:16,440
 MICROBIOME I WANTED INDICATING

1264
00:59:16,440 --> 00:59:19,720
 THAT A SINGLE SPECIES WAS

1265
00:59:19,720 --> 00:59:22,160
 INSUFFICIENT TO RECAPITULATE

1266
00:59:22,160 --> 00:59:23,720
 THE RICHNESS ACCUMULATION, THE

1267
00:59:23,720 --> 00:59:25,640
 NUMBER AND TYPES OF ORGANISMS

1268
00:59:25,640 --> 00:59:29,880
 NECESSARY IN A HEALTHY GUT

1269
00:59:29,880 --> 00:59:30,920
 MICROBIOME.

1270
00:59:30,920 --> 00:59:32,840
 NONETHELESS, WHAT WE DID SHOW

1271
00:59:32,840 --> 00:59:34,320
 WAS THE SUPPLEMENTED INFANTS,

1272
00:59:34,320 --> 00:59:37,360
 AFTER THREE MONTHS OF DAILY

1273
00:59:37,360 --> 00:59:39,240
 SUPPLEMENTATION DEMONSTRATES A

1274
00:59:39,240 --> 00:59:41,280
 GUT MICROBIOME THAT WAS

1275
00:59:41,280 --> 00:59:42,800
 SIGNIFICANTLY MORE LIKE THAT

1276
00:59:42,800 --> 00:59:44,200
 OF THE HEALTHY CONTROL

1277
00:59:44,200 --> 00:59:46,440
 POPULATION AND THAT WAS EVEN

1278
00:59:46,440 --> 00:59:48,000
 MORE PRONOUNCED BY SIX MONTHS

1279
00:59:48,000 --> 00:59:48,640
 OF AGE.

1280
00:59:48,640 --> 00:59:51,640
 BUT BY NINE MONTHS OF AGE,

1281
00:59:51,640 --> 00:59:53,240
 THIS SIMILARITY HAS BEEN LOST

1282
00:59:53,240 --> 00:59:57,800
 AND BY 12 MONTHS OF AGE, WE

1283
00:59:57,800 --> 00:59:59,880
 SEE THIS SNEAK BACK IN AND NOT

1284
00:59:59,880 --> 01:00:02,840
 SURE WHY THIS OCCURRED.

1285
01:00:02,840 --> 01:00:12,640
 WHEN WE LOOKED AT TARGETED 

1286
01:00:12,640 --> 01:00:14,240
 METABOLO MIC, THE HIGH RISK

1287
01:00:14,240 --> 01:00:18,360
 GROUP HAD A MORE SIMILAR FECAL

1288
01:00:18,360 --> 01:00:20,520
 METABOLOME COMPARED TO HEALTHY

1289
01:00:20,520 --> 01:00:22,360
 INFANTS BUT AGAIN THIS WAS BY

1290
01:00:22,360 --> 01:00:24,440
 12 MONTHS OF AGE, PERHAPS

1291
01:00:24,440 --> 01:00:26,800
 EXPLAINING WHY WE SAW NO

1292
01:00:26,800 --> 01:00:27,520
 SIGNIFICANT DINNERS IN COULD

1293
01:00:27,520 --> 01:00:29,800
 YOU TELL COME AT THREE YEARS

1294
01:00:29,800 --> 01:00:30,480
 OF AGE.

1295
01:00:30,480 --> 01:00:32,120
 HERE I WILL WALK YOU THROUGH

1296
01:00:32,120 --> 01:00:34,040
 SORT OF THE DETAILS OF THE

1297
01:00:34,040 --> 01:00:39,040
 FEATURES OF THE FECAL META

1298
01:00:39,040 --> 01:00:40,000
 BOLOME THAT CHARACTERIZED

1299
01:00:40,000 --> 01:00:42,280
 THESE INFANTS WHO HAD BEEN

1300
01:00:42,280 --> 01:00:42,720
 SUPPLEMENTED.

1301
01:00:42,720 --> 01:00:44,480
 AND WHAT I AM SHOWING YOU HERE

1302
01:00:44,480 --> 01:00:50,480
 IS IN THE WARMER COLORS, THE

1303
01:00:50,480 --> 01:00:51,640
 METABOLITES WERE ENRICHED IN

1304
01:00:51,640 --> 01:00:53,640
 THE HIGH RISK PLACEBO GROUP

1305
01:00:53,640 --> 01:00:55,240
 COMPARED TO THE HEALTHY

1306
01:00:55,240 --> 01:01:06,960
 CONTROL OR THE HIGH RISK 

1307
01:01:06,960 --> 01:01:08,040
 LACKED -- LACTOBACILLUS

1308
01:01:08,040 --> 01:01:10,720
 SUPPLEMENTED BABIES. 

1309
01:01:10,720 --> 01:01:15,240
 SO WE CAN SEE THE GUT

1310
01:01:15,240 --> 01:01:18,440
 MICROBIOME IN BOTH HIGH RISK

1311
01:01:18,440 --> 01:01:27,360
 BABIES ASSOCIATED WITH A RANGE

1312
01:01:27,360 --> 01:01:29,720
 OF INFLAMMATORY MONOHYDROXIDE

1313
01:01:29,720 --> 01:01:32,840
 FATTY ACIDS BY CODES.

1314
01:01:32,840 --> 01:01:34,880
 IN COMPARISON, INFANTS WHO

1315
01:01:34,880 --> 01:01:36,600
 RECEIVED SIX MONTHS OF

1316
01:01:36,600 --> 01:01:37,800
 SUPPLEMENTATION, AS YOU CAN

1317
01:01:37,800 --> 01:01:40,480
 SEE CLEARLY, THERE IS QUITE A

1318
01:01:40,480 --> 01:01:42,440
 LOT OF OVERLAP IN TERMS OF THE

1319
01:01:42,440 --> 01:01:44,080
 LIPIDS AND HAD STEROIDS

1320
01:01:44,080 --> 01:01:48,560
 PRODUCED IN THAT FECAL

1321
01:01:48,560 --> 01:01:51,080
 METABOLOME -- OR PRESENT IN

1322
01:01:51,080 --> 01:01:54,000
 THAT THAT OVERLAP THE HEALTHY

1323
01:01:54,000 --> 01:01:55,520
 CONTROLLED CHILDREN.

1324
01:01:55,520 --> 01:01:59,560
 WHICH MEANS THE PROBIOTIC

1325
01:01:59,560 --> 01:02:03,360
 INTRODUCTION REALLY HAD A

1326
01:02:03,360 --> 01:02:06,040
 PROFOUND EFFECT IN THE SPECIES

1327
01:02:06,040 --> 01:02:07,400
 OF THESE INFANTS.

1328
01:02:07,400 --> 01:02:10,240
 AND AMONG THOSE LIPIDS WERE A

1329
01:02:10,240 --> 01:02:14,240
 LARGE NUMBER OF HIGHLY

1330
01:02:14,240 --> 01:02:15,600
 INFLAMMATORY FATTY ACIDS.

1331
01:02:15,600 --> 01:02:17,920
 SO BY INTRODUCING THIS DAILY

1332
01:02:17,920 --> 01:02:19,800
 FOR THE FIRST SIX MONTHS OF

1333
01:02:19,800 --> 01:02:22,760
 LIFE, IT COULD REALLY

1334
01:02:22,760 --> 01:02:24,040
 REENGINEER METABOLISM IN THE

1335
01:02:24,040 --> 01:02:26,080
 FECES OF THESE INFANTS.

1336
01:02:26,080 --> 01:02:30,240
 BUT THESE ARE SIMPLY

1337
01:02:30,240 --> 01:02:31,640
 CORRELATIONS, METABOLITES THAT

1338
01:02:31,640 --> 01:02:33,200
 ARE ENRICHED IN THESE INFANTS.

1339
01:02:33,200 --> 01:02:35,000
 SO WE MOVED ON TO DETERMINE

1340
01:02:35,000 --> 01:02:41,880
 WHETHER THE PRODUCTS IN THESE

1341
01:02:41,880 --> 01:02:44,680
 MICROBIOTICS REALLY HAD AN

1342
01:02:44,680 --> 01:02:46,800
 EFFECT ON THE IMMUNE SYSTEM

1343
01:02:46,800 --> 01:02:47,480
 RELATED TO ASTHMA.

1344
01:02:47,480 --> 01:02:51,360
 SO HERE YOU HAVE THE ASTHMA IN

1345
01:02:51,360 --> 01:02:54,240
 CHILDREN, ASSOCIATED WITH

1346
01:02:54,240 --> 01:02:59,600
 REDUCED REGULATORY T SKRELS,

1347
01:02:59,600 --> 01:03:01,880
 INCREASED TH2 CELLS AND IGE.

1348
01:03:01,880 --> 01:03:05,880
 SO IF YOU LOOK AT THE CELLS

1349
01:03:05,880 --> 01:03:10,320
 FROM HEALTHY ADULT OWNERS THAT

1350
01:03:10,320 --> 01:03:13,040
 DICTATE THE T CELLS AND THEIR

1351
01:03:13,040 --> 01:03:17,040
 PHENOTYPE BUT WE USE THE CELL

1352
01:03:17,040 --> 01:03:18,440
 FREE PRODUCTS WITH INFANTS IN

1353
01:03:18,440 --> 01:03:22,480
 THE TRIAL TO DETERMINE HOW

1354
01:03:22,480 --> 01:03:27,640
 THEY WILL INFLUENCE THE

1355
01:03:27,640 --> 01:03:31,240
 DENDRITIC AND T CELL IMMUNITY

1356
01:03:31,240 --> 01:03:31,760
 IN VITRO.

1357
01:03:31,760 --> 01:03:35,840
 AND WHAT WE COULD SEE IS AFTER

1358
01:03:35,840 --> 01:03:37,880
 SIX MONTHS OF SUPPLEMENTATION

1359
01:03:37,880 --> 01:03:41,280
 WHERE WE SAW THE TINY INCREASE

1360
01:03:41,280 --> 01:03:44,440
 IN T CELLS AND LIPIDS, WE SAW

1361
01:03:44,440 --> 01:03:47,560
 A BIG INCREASE IN FREQUENCY

1362
01:03:47,560 --> 01:03:50,640
 COMPARED TO THE PLACEBO GROUP

1363
01:03:50,640 --> 01:03:53,120
 AND THE HEALTHY GROUP.

1364
01:03:53,120 --> 01:03:55,520
 BY 12 MONTHS, WE SAW NO

1365
01:03:55,520 --> 01:03:57,480
 SIGNIFICANT DIFFERENCE IN

1366
01:03:57,480 --> 01:03:59,440
 REGISTERED T CELLS FREQUENCY

1367
01:03:59,440 --> 01:04:02,200
 IN THESE GROUPS AND THAT AGAIN

1368
01:04:02,200 --> 01:04:04,120
 WAS ASSISTED WITH THE SHIFT

1369
01:04:04,120 --> 01:04:07,400
 BACK TOWARDS FECAL METABOLOMES

1370
01:04:07,400 --> 01:04:10,040
 THAT REALLY IS QUITE LIKE THAT

1371
01:04:10,040 --> 01:04:15,160
 OF THE PREVIOUSLY

1372
01:04:15,160 --> 01:04:16,280
 PLACEBO-SUPPLEMENTED INFANT

1373
01:04:16,280 --> 01:04:18,640
 SUGGESTING WHILE THE

1374
01:04:18,640 --> 01:04:19,400
 SUPPLEMENTATION IS OCCURRING,

1375
01:04:19,400 --> 01:04:24,000
 THERE IS A REENGINEERING OF

1376
01:04:24,000 --> 01:04:25,520
 THE METABOLOME THAT HAS AN

1377
01:04:25,520 --> 01:04:27,160
 EFFECT ON THE IMMUNE FUNCTION.

1378
01:04:27,160 --> 01:04:31,840
 AND HERE SUE CAN SEE THE

1379
01:04:31,840 --> 01:04:33,640
 LACTOBACILLUS WEREN'T IN THESE

1380
01:04:33,640 --> 01:04:35,000
 INFANTS AND TESTIMONIES

1381
01:04:35,000 --> 01:04:37,920
 STRAIGHTS THAT LACK OF IT IN

1382
01:04:37,920 --> 01:04:44,360
 INFANTS 6 AND 12 MONTHS OF AGE

1383
01:04:44,360 --> 01:04:46,520
 SHOWS AS SIGNIFICANT.

1384
01:04:46,520 --> 01:04:49,520
 SO A BIT LATER IN THE YEAR A

1385
01:04:49,520 --> 01:04:50,680
 PAPER PRO SPRAYEDD US WITH A

1386
01:04:50,680 --> 01:04:54,320
 BETTER VIEW OF HOW THE

1387
01:04:54,320 --> 01:04:58,000
 PROBIOTIC STRAINS WORK ON 

1388
01:04:58,000 --> 01:04:58,520
 SUPPLEMENTATION OF

1389
01:04:58,520 --> 01:04:58,920
 INDIVIDUALS.

1390
01:04:58,920 --> 01:05:00,840
 THIS IS THE STUDY FROM THE LM

1391
01:05:00,840 --> 01:05:03,040
 GROUP AND THEY SUPPLEMENTED

1392
01:05:03,040 --> 01:05:05,440
 HEALTHY ADULTS WITH A COCKTAIL

1393
01:05:05,440 --> 01:05:08,800
 OF 11 COMMONLY USED PROBIOTIC

1394
01:05:08,800 --> 01:05:09,480
 SPECIES, FOLLOWED THESE

1395
01:05:09,480 --> 01:05:11,480
 INDIVIDUALS OVER TIME AND

1396
01:05:11,480 --> 01:05:12,120
 SEAMED THEM EXTENSIVELY.

1397
01:05:12,120 --> 01:05:13,440
 AND WHAT YOU CAN SEE

1398
01:05:13,440 --> 01:05:15,200
 CONSISTENT WITH THEIR OWN

1399
01:05:15,200 --> 01:05:17,800
 OBSERVATIONS IS DURING THE

1400
01:05:17,800 --> 01:05:18,800
 SUPPLEMENTATION PERIOD, MANY

1401
01:05:18,800 --> 01:05:24,800
 OF THE PRO BIOTICS ARE IN THE

1402
01:05:24,800 --> 01:05:26,280
 FECES BUT AFTER THE

1403
01:05:26,280 --> 01:05:28,000
 SUPPLEMENTATION, THEY ARE NOT

1404
01:05:28,000 --> 01:05:35,120
 FOUND WHICH SUGGESTS THERE ARE

1405
01:05:35,120 --> 01:05:36,680
 REALLY POOR BIOTIC STRAINS IN

1406
01:05:36,680 --> 01:05:41,560
 THE PASS  GASTROINTESTINAL

1407
01:05:41,560 --> 01:05:42,080
 TRACK.

1408
01:05:42,080 --> 01:05:46,240
 THEY WENT ON TO SHOW THE

1409
01:05:46,240 --> 01:05:49,240
 LOCATIONS OF THE PROBIOTIC

1410
01:05:49,240 --> 01:05:51,600
 SPECIES THAT HAVE A PREVALENCE

1411
01:05:51,600 --> 01:05:54,080
 ALONG THE GI TRACT THEY PREFER

1412
01:05:54,080 --> 01:05:55,240
 TO COLONIZE.

1413
01:05:55,240 --> 01:05:59,000
 YOU CAN SEE A HEIGHTENED

1414
01:05:59,000 --> 01:06:01,120
 ABUNDANCE OF THEM AT SPECIFIC

1415
01:06:01,120 --> 01:06:05,160
 SITES SO THE REGION OF STRAINS

1416
01:06:05,160 --> 01:06:08,520
 FOR THESE ORGANISMS CONTRIBUTE

1417
01:06:08,520 --> 01:06:09,040
 TO MUCOSA.

1418
01:06:09,040 --> 01:06:12,400
 FOR THE STUDY, THE CAPACITY OF

1419
01:06:12,400 --> 01:06:16,440
 REDUCED ORGANISMS TO COLONIZE

1420
01:06:16,440 --> 01:06:19,840
 WERE REALLY LINKED TO WHETHER

1421
01:06:19,840 --> 01:06:21,240
 THERE WERE RELATED COMPETITIVE

1422
01:06:21,240 --> 01:06:23,040
 STRAINS AT THAT SITE.

1423
01:06:23,040 --> 01:06:35,800
 SO IF THE ORGANISMS FOUND A 

1424
01:06:35,800 --> 01:06:37,600
 NICHE IN WHICH THEY WERE

1425
01:06:37,600 --> 01:06:39,440
 COMPATIBLE WITH OTHER PIECE

1426
01:06:39,440 --> 01:06:41,040
 SEES, THEY WERE LIKELY FOUND

1427
01:06:41,040 --> 01:06:42,560
 IN THAT SITE.

1428
01:06:42,560 --> 01:06:45,640
 THE PRESENCE OF THE ORGANISMS,

1429
01:06:45,640 --> 01:06:57,240
 DID CHANGE THE

1430
01:06:57,240 --> 01:06:58,040
 TRANSCRIPTAL MUCOSAL PATTERNS

1431
01:06:58,040 --> 01:07:01,320
 AND THEY HAD THE EARLY

1432
01:07:01,320 --> 01:07:02,600
 COLONIZATION AND THE

1433
01:07:02,600 --> 01:07:04,440
 INTRODUCTION OF PRO BY YACHT

1434
01:07:04,440 --> 01:07:09,760
 TICKS LED TO CHANGES IN T CELL

1435
01:07:09,760 --> 01:07:12,040
 RESPONSES AND INFLAMMATORY

1436
01:07:12,040 --> 01:07:14,880
 RESPONSES AND THOSE WITH THE

1437
01:07:14,880 --> 01:07:17,800
 OTHER INTRODUCTION HAD A

1438
01:07:17,800 --> 01:07:21,280
 CHANGE IN T CELLS AND RECEPTOR

1439
01:07:21,280 --> 01:07:23,640
 PATHWAYS THAT PERHAPS, THE

1440
01:07:23,640 --> 01:07:25,560
 INTRINSIC FACTORS PLAY A ROLE

1441
01:07:25,560 --> 01:07:27,800
 FROM PREVENTING THE ORGANISMS

1442
01:07:27,800 --> 01:07:31,320
 FROM COLONIZING THE NICHE.

1443
01:07:31,320 --> 01:07:37,120
 AND IT MAY BE LIMITED IN

1444
01:07:37,120 --> 01:07:38,400
 UNIVERSALITY AND PERSISTENTLY

1445
01:07:38,400 --> 01:07:41,440
 IMPACT THE GUT MUCOSA AND SO

1446
01:07:41,440 --> 01:07:42,680
 SUGGESTING PERHAPS WE SHOULD

1447
01:07:42,680 --> 01:07:47,040
 BE THINKING BY DEVELOPING NEW

1448
01:07:47,040 --> 01:07:48,000
 AND PERSONALIZED PROBIOTIC

1449
01:07:48,000 --> 01:07:50,840
 APPROACHES FOR TREATMENT FOR A

1450
01:07:50,840 --> 01:07:51,440
 NUMBER OF CONDITIONS.

1451
01:07:51,440 --> 01:07:54,040
 >> YOU HAVE ABOUT TWO MINUTES.

1452
01:07:54,040 --> 01:07:54,840
 >> PERFECT, THANK YOU.

1453
01:07:54,840 --> 01:07:58,080
 AND JUST TO THINK ABOUT HOW WE

1454
01:07:58,080 --> 01:07:58,840
 INTRODUCE AND INCORPORATE

1455
01:07:58,840 --> 01:08:04,160
 THESE KINDS OF APPROACHES INTO

1456
01:08:04,160 --> 01:08:05,320
 OUR PROBIOTIC TRIALS, THE KEY

1457
01:08:05,320 --> 01:08:09,640
 IS TO HAVE STANDARDIZED

1458
01:08:09,640 --> 01:08:12,040
 DEMOGRAPHIC, CLINICAL AND

1459
01:08:12,040 --> 01:08:12,720
 BIOSPECIMEN COLLECTIONS, BOTH

1460
01:08:12,720 --> 01:08:14,840
 IN THE PRE, PERI AND POST

1461
01:08:14,840 --> 01:08:16,080
 SUPPLEMENTATION PERIODS AND I

1462
01:08:16,080 --> 01:08:17,200
 AM NOT SUGGESTING BY THIS

1463
01:08:17,200 --> 01:08:19,120
 THERE IS A EXAMINER IN EACH OF

1464
01:08:19,120 --> 01:08:21,840
 THESE TIME LINES BUT THAT WE

1465
01:08:21,840 --> 01:08:27,640
 DO LOOK ACROSS THESE THREE

1466
01:08:27,640 --> 01:08:27,920
 TYPES.

1467
01:08:27,920 --> 01:08:34,040
 HERE WOULD YOU HAVE THE

1468
01:08:34,040 --> 01:08:35,080
 SPECIMEN, SKIN SAMPLES

1469
01:08:35,080 --> 01:08:36,840
 CONDITIONING ON WHAT IS BEING

1470
01:08:36,840 --> 01:08:38,440
 CONSIDERED AND PARALLEL WITH

1471
01:08:38,440 --> 01:08:39,760
 BLOOD SAMPLES TO ALLOW

1472
01:08:39,760 --> 01:08:43,960
 ASSESSMENT OF A RANGE OF STATE

1473
01:08:43,960 --> 01:08:44,680
 OF MODALITY.

1474
01:08:44,680 --> 01:08:46,920
 THESE SAMPLES NEED TO BE

1475
01:08:46,920 --> 01:08:48,240
 PROCESSED AT THE TIME OF

1476
01:08:48,240 --> 01:08:51,040
 COLLECTION AS PRESERVED AND

1477
01:08:51,040 --> 01:08:52,800
 UNPRESERVED FRACTIONS TO ALLOW

1478
01:08:52,800 --> 01:08:56,680
 THE AS SIT ANALYSIS, DNA AND

1479
01:08:56,680 --> 01:09:01,720
 RNA BASED ANALYSIS TO

1480
01:09:01,720 --> 01:09:02,320
 UNDERSTAND TRANSCRIPTAL

1481
01:09:02,320 --> 01:09:06,640
 DIVERSITY BOTH OF THE HOST AND

1482
01:09:06,640 --> 01:09:09,280
 MICROBIOME TO ALLOW US TO

1483
01:09:09,280 --> 01:09:14,680
 FACILITATE THE APPROACHES AND 

1484
01:09:14,680 --> 01:09:18,040
 REALLY FUNCTIONAL ASSAYS, LIKE

1485
01:09:18,040 --> 01:09:22,560
 THE IMMUNE ASSAYS, THE MASS

1486
01:09:22,560 --> 01:09:24,960
 SPECTOMETRY ANALYSIS TO ALLOW

1487
01:09:24,960 --> 01:09:36,400
 THE MICROBIOME ON PHYSICAL

1488
01:09:36,400 --> 01:09:37,040
 LOGICAL FEATURES IN VITRO.

1489
01:09:37,040 --> 01:09:37,680
 AND ULTIMATELY WHAT WOULD BE

1490
01:09:37,680 --> 01:09:38,320
 IDEAL IS FOR ALL THIS DATA

1491
01:09:38,320 --> 01:09:39,000
 FROM THESE TRIALS TO BE AS

1492
01:09:39,000 --> 01:09:40,560
 MENTIONED, LOCATED IN A DATA

1493
01:09:40,560 --> 01:09:41,960
 LIBRARY, TO BE A RESOURCE FOR

1494
01:09:41,960 --> 01:09:43,800
 US TO CONTINUE TO UNDERSTAND

1495
01:09:43,800 --> 01:09:44,840
 WHO RESPONDS, HOW THEY

1496
01:09:44,840 --> 01:09:47,720
 RESPOND, THE FEATURES OF THOSE

1497
01:09:47,720 --> 01:09:51,440
 WHO MAY BE RESPONSIVE TO

1498
01:09:51,440 --> 01:09:51,920
 SPECIFIC PROBIOTIC

1499
01:09:51,920 --> 01:09:53,480
 SUPPLEMENTATION AND THIS IS

1500
01:09:53,480 --> 01:09:56,800
 KIND OF DATA THAT WILL BE

1501
01:09:56,800 --> 01:09:58,760
 FACILITATED BY MACHINE

1502
01:09:58,760 --> 01:09:59,880
 LEARNING APPROACHES AS HAS

1503
01:09:59,880 --> 01:10:00,960
 BEEN MENTIONED.

1504
01:10:00,960 --> 01:10:03,040
 SO I WILL LIKE TO THANK THOSE

1505
01:10:03,040 --> 01:10:05,120
 WHOSE WORK I SHARED WITH YOU

1506
01:10:05,120 --> 01:10:07,160
 TODAY, A NUMB OF INDIVIDUALS

1507
01:10:07,160 --> 01:10:10,360
 IN OUR GROUP WHO MADE OUR

1508
01:10:10,360 --> 01:10:36,560
 STUDIES POSSIB

1509
01:10:36,560 --> 01:10:42,400
THANKS TO THE ORGANIZERS I WILL

1510
01:10:42,400 --> 01:10:44,840
GIVE A LITTLE BIT OF AN

1511
01:10:44,840 --> 01:10:49,880
OVERVIEW WHERE THAT GOT

1512
01:10:49,880 --> 01:10:50,440
MICROBIOTA HAS TAUGHT ABOUT

1513
01:10:50,440 --> 01:10:55,200
THE GUT INTERACTIONS BETWEEN

1514
01:10:55,200 --> 01:10:56,840
THE BRAIN AND WE HAVE BEEN

1515
01:10:56,840 --> 01:10:57,280
ABLE TO HARNESS THAT

1516
01:10:57,280 --> 01:10:58,760
INFORMATION TO DROP THAT

1517
01:10:58,760 --> 01:11:05,240
INTERACTION SO VERY QUICKLY

1518
01:11:05,240 --> 01:11:17,320
THERE ARE CONDUITS SO THE

1519
01:11:17,320 --> 01:11:21,800
CHEMICAL COMMUNICATION THAT

1520
01:11:21,800 --> 01:11:26,920
ARE TRANSFORMED IN THE LIVER

1521
01:11:26,920 --> 01:11:32,120
AND IMPACT BEHAVIOR.

1522
01:11:32,120 --> 01:11:35,720
THE CONTEXT HERE IS SPECTERS

1523
01:11:35,720 --> 01:11:39,560
ON OUR SPECTRUM DISORDER.

1524
01:11:39,560 --> 01:11:49,040
AND THEN IS DIAGNOSED.

1525
01:11:49,040 --> 01:11:49,840
THERE ARE A NUMBER OF

1526
01:11:49,840 --> 01:11:59,520
COMORBIDITIES FOR AUTISM THAT

1527
01:11:59,520 --> 01:12:00,720
ALSO IMMUNE DYSFUNCTION WHERE

1528
01:12:00,720 --> 01:12:05,120
ALL OF THE VALLEYS THAT ARE

1529
01:12:05,120 --> 01:12:10,680
IMPACTED.

1530
01:12:10,680 --> 01:12:26,680
 

1531
01:13:20,040 --> 01:13:20,480
 IT GETS ACROSS THE

1532
01:13:20,480 --> 01:13:24,200
EPITHELIUM AND THEN IS IN THE

1533
01:13:24,200 --> 01:13:25,040
LIVER.

1534
01:13:25,040 --> 01:13:30,720
THIS IS A RELATED COMPOUND AND

1535
01:13:30,720 --> 01:13:33,200
THEN TO BE ELEVATED IN HUMAN

1536
01:13:33,200 --> 01:13:40,280
AUTISM THAT IS IN THE COHORT

1537
01:13:40,280 --> 01:13:41,280
WITH THE SAME CHEMICAL

1538
01:13:41,280 --> 01:13:42,600
CATEGORY WE WILL COME BACK TO

1539
01:13:42,600 --> 01:13:45,800
THIS TREATMENT THAT

1540
01:13:45,800 --> 01:13:46,840
ESSENTIALLY NEUTRALIZES ALL OF

1541
01:13:46,840 --> 01:13:50,280
THE METABOLITES.

1542
01:13:50,280 --> 01:13:57,600
SO I MENTIONED AND TO PRODUCE

1543
01:13:57,600 --> 01:14:00,960
THAT AND OF COURSE YOU WANT TO

1544
01:14:00,960 --> 01:14:03,440
TRANSLATE THIS TO HUMANS AND

1545
01:14:03,440 --> 01:14:06,120
WE PUBLISH THE DATA SET PATH

1546
01:14:06,120 --> 01:14:12,280
FROM SAMPLES GIVEN TO US WHERE

1547
01:14:12,280 --> 01:14:14,720
THEY HAD COLLECTED PLASMA AND

1548
01:14:14,720 --> 01:14:17,840
FECES THAT ARE TYPICALLY

1549
01:14:17,840 --> 01:14:19,800
DEVELOPING INDIVIDUALS TO A

1550
01:14:19,800 --> 01:14:27,800
LARGE DATA SET AND THEN ONE

1551
01:14:27,800 --> 01:14:33,520
THIRD OF THE INDIVIDUALS AND

1552
01:14:33,520 --> 01:14:36,040
ABOUT ONE THIRD OF THESE WITH

1553
01:14:36,040 --> 01:14:37,600
AUTISM THOSE HAVE

1554
01:14:37,600 --> 01:15:38,000
GASTROINTESTINAL SYMPTOMS AND
THEN

1555
01:15:38,000 --> 01:15:40,520
THEY ENGINEERED STRAINS TO

1556
01:15:40,520 --> 01:15:42,080
PRODUCE WITH THOSE BACTERIAL

1557
01:15:42,080 --> 01:15:45,080
STRAINS ARE IDENTICAL EXCEPT

1558
01:15:45,080 --> 01:15:48,520
THE EP POSITIVE BACTERIA TO

1559
01:15:48,520 --> 01:15:57,040
HAVE THESE GENES AND THEN THE

1560
01:15:57,040 --> 01:16:02,720
SAME BACTERIAL SPECIES THAT DO

1561
01:16:02,720 --> 01:16:03,080
NOT CONTAIN.

1562
01:16:03,080 --> 01:16:03,600
SO THAN THE COLONIZED TWO

1563
01:16:03,600 --> 01:16:08,240
GROUPS OF MICE WHETHER THE

1564
01:16:08,240 --> 01:16:10,560
NEGATIVE GROUP OR THE POSITIVE

1565
01:16:10,560 --> 01:16:12,120
GROUP THAT DISTINGUISHES THESE

1566
01:16:12,120 --> 01:16:17,480
TWO GROUPS OF MICE AND THEN WE

1567
01:16:17,480 --> 01:16:20,680
VALIDATED WE COULD ELEVATE FOR

1568
01:16:20,680 --> 01:16:22,880
EP IN THE FECES OF THESE

1569
01:16:22,880 --> 01:16:25,640
ANIMALS IN THE CIRCULATION

1570
01:16:25,640 --> 01:16:27,320
SHOWING HERE WITH LOSS OF

1571
01:16:27,320 --> 01:16:30,040
BLOOD THAT WE CAN DETECT AND

1572
01:16:30,040 --> 01:16:36,880
IF WE BLOCK EXPORTS WE WILL

1573
01:16:36,880 --> 01:16:37,440
SEE A BUILDUP OF EPS IN THE

1574
01:16:37,440 --> 01:16:37,920
BRAINS OF THESE ANIMALS.

1575
01:16:37,920 --> 01:16:40,480
WE DON'T DETECT MUCH FOR THE

1576
01:16:40,480 --> 01:16:43,600
CIRCULATION WITH A

1577
01:16:43,600 --> 01:16:45,440
QUANTITATIVE CONVERSION AND

1578
01:16:45,440 --> 01:16:51,720
OTHER LINES OF EVIDENCE.

1579
01:16:51,720 --> 01:16:56,720
SO WE SHOWED THE BRAIN

1580
01:16:56,720 --> 01:17:06,240
ACTIVITY AND ANYTHING IN RED

1581
01:17:06,240 --> 01:17:11,080
IS MORE ACTIVE FOR THOSE WHO

1582
01:17:11,080 --> 01:17:14,600
UNDERSTAND THE ANATOMY OF THE

1583
01:17:14,600 --> 01:17:15,640
BRAIN THIS IS A PART OF THE

1584
01:17:15,640 --> 01:17:18,760
LIMBIC SYSTEM WITH EMOTIONAL

1585
01:17:18,760 --> 01:17:21,080
BEHAVIOR AND REGULATION THERE

1586
01:17:21,080 --> 01:17:25,840
ARE A NUMBER THAT ARE LESS

1587
01:17:25,840 --> 01:17:26,720
ACTIVE WE DON'T HAVE TIME TO

1588
01:17:26,720 --> 01:17:28,000
SHOW IS THE CHANGE OF

1589
01:17:28,000 --> 01:17:32,680
CONDUCTIVITY WHICH HAS BEEN

1590
01:17:32,680 --> 01:17:35,200
SHOWN AND MOUSE MODELS.

1591
01:17:35,200 --> 01:17:42,240
>> WE WANT TO UNDERSTAND HOW

1592
01:17:42,240 --> 01:17:43,320
THE BRAIN REGIONS CHANGES AND

1593
01:17:43,320 --> 01:17:49,840
MANIFESTS REGULAR OR MOLECULAR

1594
01:17:49,840 --> 01:17:50,400
SO WITH SIX DIFFERENT BRAIN

1595
01:17:50,400 --> 01:17:52,520
REGIONS AND THE PIE CHART

1596
01:17:52,520 --> 01:17:55,520
SHOWS GENES IN SIX OF THESE

1597
01:17:55,520 --> 01:17:57,760
REGIONS THIS IS THE REGION

1598
01:17:57,760 --> 01:18:04,600
THAT IS MOST EFFECTIVE AND

1599
01:18:04,600 --> 01:18:05,200
THOSE THAT WERE IN THIS REGION

1600
01:18:05,200 --> 01:18:09,240
THAT IS PRETTY INTERESTING AND

1601
01:18:09,240 --> 01:18:17,200
THEN THE PANEL ON THE BOTTOM

1602
01:18:17,200 --> 01:18:21,960
BUT ALSO ON THE PRECURSORS AND

1603
01:18:21,960 --> 01:18:25,200
THAT'S WHAT YOU SEE IN THE OPC

1604
01:18:25,200 --> 01:18:26,200
IMAGE.

1605
01:18:26,200 --> 01:18:31,320
SO THEN WE WENT TO VALIDATE.

1606
01:18:31,320 --> 01:18:33,680
AND THEN SPECIFIC FOR THOSE

1607
01:18:33,680 --> 01:18:40,080
PRECURSOR CELLS.

1608
01:18:40,080 --> 01:18:40,520
AND THOSE THAT DO HAVE

1609
01:18:40,520 --> 01:18:43,680
PRECURSORS ARE ELEVATED AND ON

1610
01:18:43,680 --> 01:18:48,200
THE RIGHT SIDE YOU CAN SEE

1611
01:18:48,200 --> 01:18:49,840
WITH THAT EXPRESSION OF GENES

1612
01:18:49,840 --> 01:18:51,480
THAT ARE ASSOCIATED.

1613
01:18:51,480 --> 01:18:56,920
SO IT REALLY LOOKS LIKE IN ALL

1614
01:18:56,920 --> 01:18:58,000
THE MATURATION AND AFTER THEY

1615
01:18:58,000 --> 01:19:05,280
TOLD US.

1616
01:19:05,280 --> 01:19:06,000
AND THEN TO LOOK AT SURFACE

1617
01:19:06,000 --> 01:19:13,120
MARKERS TO DIFFERENTIATE AND

1618
01:19:13,120 --> 01:19:14,080
THEN YOU CAN SEE ON THE LEFT

1619
01:19:14,080 --> 01:19:19,000
BARS THAT QUOTIENT FOR EP

1620
01:19:19,000 --> 01:19:21,920
POSITIVE WHERE THIS INCREASED

1621
01:19:21,920 --> 01:19:25,080
TO THE NEGATIVE GROWTH SHOWING

1622
01:19:25,080 --> 01:19:26,000
THAT THERE ARE MANY LESS

1623
01:19:26,000 --> 01:19:29,920
MATURE SITES PER VOLUME TO

1624
01:19:29,920 --> 01:19:36,320
THAT THERE ARE NO DIFFERENCES

1625
01:19:36,320 --> 01:19:36,880
SO WE PROPOSE THAT THEY ARE

1626
01:19:36,880 --> 01:19:37,440
THERE BUT THOSE ARE

1627
01:19:37,440 --> 01:19:40,360
DIFFERENCES THAT THERE IS A

1628
01:19:40,360 --> 01:19:42,480
RESTRAINT IN THE MATURATION.

1629
01:19:42,480 --> 01:19:45,560
ALSO FOR THOSE WHERE WE LOOKED

1630
01:19:45,560 --> 01:19:49,720
AT ADDITIONAL MARKERS LOOKING

1631
01:19:49,720 --> 01:19:50,320
AT THOSE POPULATIONS OF CELLS

1632
01:19:50,320 --> 01:19:53,320
AND THEN AGAIN WITH A PROFILE

1633
01:19:53,320 --> 01:19:57,480
THAT THERE ARE LESS MATURE IN

1634
01:19:57,480 --> 01:19:58,520
THE POSITIVE GROUP VERSUS THE

1635
01:19:58,520 --> 01:20:02,920
NEGATIVE GROUP AND THIS IS THE

1636
01:20:02,920 --> 01:20:04,360
CASE AS WELL SO ALL THE SITES

1637
01:20:04,360 --> 01:20:05,240
HAVE A NUMBER OF DIFFERENT

1638
01:20:05,240 --> 01:20:11,520
FUNCTIONS THAT PRIMARILY THEY

1639
01:20:11,520 --> 01:20:14,000
HELP WITH SIGNALING ACROSS THE

1640
01:20:14,000 --> 01:20:20,000
AXONS.

1641
01:20:20,000 --> 01:20:21,040
AND WITH THAT ELECTRON

1642
01:20:21,040 --> 01:20:24,440
TOMOGRAPHY TO VISUALIZE THE

1643
01:20:24,440 --> 01:20:25,480
MYELIN WHICH IS THE SHEATH

1644
01:20:25,480 --> 01:20:26,520
THAT COVERS THE AXON LIKE THE

1645
01:20:26,520 --> 01:20:32,480
CODING ON A COPPER WIRE

1646
01:20:32,480 --> 01:20:33,040
HELPING TO TRANSMIT SIGNALS

1647
01:20:33,040 --> 01:20:33,400
LONG DISTANCES.

1648
01:20:33,400 --> 01:20:36,360
AND AGAIN WE SEE THE PANEL

1649
01:20:36,360 --> 01:20:36,920
BASED ON THE PROGRAMS THAT

1650
01:20:36,920 --> 01:20:41,680
THERE ARE MORE AXONS AND GROUP

1651
01:20:41,680 --> 01:20:49,720
A HIGHER G RATIO FOR CELL

1652
01:20:49,720 --> 01:20:51,920
STRUCTURE AND THEN WE SEE

1653
01:20:51,920 --> 01:20:53,000
THINNER MYELIN AND THAT IS IN

1654
01:20:53,000 --> 01:20:56,080
THE POSITIVE GROUP AND THEN

1655
01:20:56,080 --> 01:21:00,120
THAT WAS QUANTITATIVE AND THE

1656
01:21:00,120 --> 01:21:01,600
MYELIN IS THINNER IN THE

1657
01:21:01,600 --> 01:21:05,320
POSITIVES US ALL CONSISTENT

1658
01:21:05,320 --> 01:21:15,200
WITH MATURATION AND AND THEN

1659
01:21:15,200 --> 01:21:17,760
TO LOOK AT THE NUCLEUS OF THE

1660
01:21:17,760 --> 01:21:21,960
THALAMUS SPECIFICALLY AND THE

1661
01:21:21,960 --> 01:21:22,560
LOWER FA SCORE MEANS THERE'S

1662
01:21:22,560 --> 01:21:26,360
MORE DISORGANIZED MYELIN

1663
01:21:26,360 --> 01:21:26,960
CONSISTENT WITH THE PREDICTION

1664
01:21:26,960 --> 01:21:31,920
OF GENE EXPRESSION.

1665
01:21:31,920 --> 01:21:34,400
SO WITH THIS MATURATION WITH

1666
01:21:34,400 --> 01:21:42,800
THE MYELINATION DEFECTS.

1667
01:21:42,800 --> 01:21:43,960
SO WILL THIS PROMOTE ALTERED

1668
01:21:43,960 --> 01:21:45,720
BEHAVIOR QUICK SO USING TEST

1669
01:21:45,720 --> 01:21:49,400
FOR ANXIETY, WE CAN SHOW ON

1670
01:21:49,400 --> 01:21:55,800
THE LEFT SIDE IT ENTERS LESS

1671
01:21:55,800 --> 01:21:59,320
AS A MEASURE FOR ANXIETY AND

1672
01:21:59,320 --> 01:22:01,720
TO BE PLACED ON THE PLATFORM

1673
01:22:01,720 --> 01:22:04,960
THE MORE ANXIOUS MICE DO NOT

1674
01:22:04,960 --> 01:22:08,360
OPEN AS FREQUENTLY AS THOSE

1675
01:22:08,360 --> 01:22:08,880
THAT ARE IN THE PEANUT

1676
01:22:08,880 --> 01:22:18,280
NEGATIVE GROUP.

1677
01:22:18,280 --> 01:22:18,840
SO THERE'S A NUMBER OF OTHER

1678
01:22:18,840 --> 01:22:19,360
BEHAVIORS THAT ARE ALTERED

1679
01:22:19,360 --> 01:22:19,920
THAT ARE CONSISTENT WITH THE

1680
01:22:19,920 --> 01:22:20,880
FACT THE LIMBIC SYSTEM IS

1681
01:22:20,880 --> 01:22:22,680
INFECTED.

1682
01:22:22,680 --> 01:22:23,200
ALL OF THESE ARE EMOTIONAL

1683
01:22:23,200 --> 01:22:23,720
BEHAVIORS SO THERE IS NO

1684
01:22:23,720 --> 01:22:25,600
COGNITIVE BEHAVIOR OR CHANGE

1685
01:22:25,600 --> 01:22:34,760
IN MODAL BEHAVIOR.

1686
01:22:34,760 --> 01:22:37,720
I WILL FINISH IN A COUPLE OF

1687
01:22:37,720 --> 01:22:38,600
MINUTES.

1688
01:22:38,600 --> 01:22:41,760
SO ULTIMATELY THIS WORKING

1689
01:22:41,760 --> 01:22:42,560
HYPOTHESIS TOGETHER TO CHANGE

1690
01:22:42,560 --> 01:22:49,520
A NUMBER OF METABOLITES AND

1691
01:22:49,520 --> 01:22:55,040
THERE IS AN INCREASED WITH THE

1692
01:22:55,040 --> 01:22:58,000
PSYLLIUM AND FENNEL AND THEN

1693
01:22:58,000 --> 01:23:02,600
SULFATED AND WITH THE CELLULAR

1694
01:23:02,600 --> 01:23:04,520
AND MOLECULAR STRUCTURES AND

1695
01:23:04,520 --> 01:23:08,200
BEHAVIORS WITH WHAT WE BELIEVE

1696
01:23:08,200 --> 01:23:20,760
TO BE BRAIN SIGNALING.

1697
01:23:20,760 --> 01:23:23,440
SO WE SAID CAN WE INTERVENE

1698
01:23:23,440 --> 01:23:26,360
AND USE PROBIOTICS AS WELL TO

1699
01:23:26,360 --> 01:23:29,680
REPAIR THE EPITHELIUM AND THEN

1700
01:23:29,680 --> 01:23:35,320
TO ASK CAN WE IDENTIFY A SMALL

1701
01:23:35,320 --> 01:23:36,480
MOLECULE DRUG TO INTERFERE

1702
01:23:36,480 --> 01:23:39,640
WITH SIGNALING FROM THE BRAIN?

1703
01:23:39,640 --> 01:23:46,000
SO WE HAVE AST 120 AND THEN WE

1704
01:23:46,000 --> 01:23:48,480
SHOW TO ADMINISTER THIS DRUG

1705
01:23:48,480 --> 01:23:55,200
IMPROVES EMOTIONAL BEHAVIORS

1706
01:23:55,200 --> 01:23:56,400
THAT THEN IN A NUMBER OF

1707
01:23:56,400 --> 01:24:02,000
DIFFERENT PARADIGMS AND THEN

1708
01:24:02,000 --> 01:24:03,120
WE CAN SEE THAT CONTROL MICE

1709
01:24:03,120 --> 01:24:05,240
HAVE BEHAVIORAL CHANGES FROM

1710
01:24:05,240 --> 01:24:08,120
THE DRUG IMPROVING AND WE

1711
01:24:08,120 --> 01:24:13,600
SHOULDERS LEVELS.

1712
01:24:13,600 --> 01:24:17,760
THEN WE DESIGN SMALL CLINICAL

1713
01:24:17,760 --> 01:24:20,760
TRIAL WITH 26 ADOLESCENTS OF

1714
01:24:20,760 --> 01:24:21,800
AUTISM BETWEEN 12 AND 17 YEARS

1715
01:24:21,800 --> 01:24:25,360
OF AGE.

1716
01:24:25,360 --> 01:24:26,360
THE TRIAL INCLUDED EIGHT WEEKS

1717
01:24:26,360 --> 01:24:31,600
OF DOSING ADMINISTERING TWICE.

1718
01:24:31,600 --> 01:24:36,080
TO LOW-DOSE TO MEDIUM AND THEN

1719
01:24:36,080 --> 01:24:36,560
HIGH-DOSE AND THEN TOOK

1720
01:24:36,560 --> 01:24:37,400
BEHAVIORAL MEASUREMENTS AND

1721
01:24:37,400 --> 01:24:43,880
TISSUE SAMPLES THROUGHOUT THE

1722
01:24:43,880 --> 01:24:44,800
COURSE OF THE TRIAL AND IT'S

1723
01:24:44,800 --> 01:24:49,080
IMPORTANT TO MENTION.

1724
01:24:49,080 --> 01:24:51,680
AND INITIALLY WE SHALL

1725
01:24:51,680 --> 01:24:56,520
ENGAGEMENT AND THEY ARE ALL

1726
01:24:56,520 --> 01:25:00,560
VERY SIMILAR IN THE URINE AND

1727
01:25:00,560 --> 01:25:02,880
THE DATA AND THE PLASMA AS

1728
01:25:02,880 --> 01:25:09,040
WELL AND SO WE BELIEVE BY

1729
01:25:09,040 --> 01:25:09,600
HAVING THIS ORALLY AVAILABLE

1730
01:25:09,600 --> 01:25:11,800
BUT NOT OBSERVABLE IT DOES NOT

1731
01:25:11,800 --> 01:25:15,320
PENETRATE INTO THE CIRCULATION

1732
01:25:15,320 --> 01:25:18,120
AND IT SEQUESTERS THOSE

1733
01:25:18,120 --> 01:25:20,720
METABOLITES THEY ARE EXCRETED

1734
01:25:20,720 --> 01:25:24,800
AT THE CIRCULATORY LEVEL.

1735
01:25:24,800 --> 01:25:28,880
SO LOOKING AT CLINICAL SCORES

1736
01:25:28,880 --> 01:25:30,040
WE SEE A NUMBER OF DIFFERENT

1737
01:25:30,040 --> 01:25:32,720
BEHAVIORAL IMPROVEMENTS FOR

1738
01:25:32,720 --> 01:25:40,040
ANXIETY AND VULNERABILITY.

1739
01:25:40,040 --> 01:25:41,600
AND YOU CAN SEE MANY OF THE

1740
01:25:41,600 --> 01:25:47,720
INDIVIDUALS WITHIN A WEEK

1741
01:25:47,720 --> 01:25:50,240
PERIOD AND THEN TO SEE A VERY

1742
01:25:50,240 --> 01:25:52,640
NICE DECREASE WITH A TOTAL

1743
01:25:52,640 --> 01:25:56,120
POPULATION BUT ALSO THE RIGHT

1744
01:25:56,120 --> 01:25:58,440
HAND PANEL IN THOSE

1745
01:25:58,440 --> 01:26:01,760
INDIVIDUALS MANY IMPROVED IN

1746
01:26:01,760 --> 01:26:06,480
EIGHT WEEKS AND THERE WAS A

1747
01:26:06,480 --> 01:26:07,040
FOUR WEEK WASHOUT SO THAN TO

1748
01:26:07,040 --> 01:26:08,560
STOP THE DRUGS AND FOUR WEEKS

1749
01:26:08,560 --> 01:26:11,120
LATER MANY SYMPTOMS HAVE

1750
01:26:11,120 --> 01:26:13,960
REBOUNDED.

1751
01:26:13,960 --> 01:26:19,720
SO THIS IS A CONCEPT TO HAVE

1752
01:26:19,720 --> 01:26:22,120
IMPROVEMENTS HAVE BEHAVIORAL

1753
01:26:22,120 --> 01:26:24,680
OUTCOMES WHICH IS VERY MUCH A

1754
01:26:24,680 --> 01:26:29,720
CONCEPT AND THEN FINALLY THE

1755
01:26:29,720 --> 01:26:33,560
ACKNOWLEDGMENT SLIDE AND

1756
01:26:33,560 --> 01:26:36,080
HIGHLY COLLABORATIVE TO HELP

1757
01:26:36,080 --> 01:26:40,480
US ALONG THE WAY SORRY I WENT

1758
01:26:40,480 --> 01:26:50,720
A COUPLE MINUTES OVER.

1759
01:26:50,720 --> 01:26:51,240
>> JUST A REMINDER DON'T

1760
01:26:51,240 --> 01:26:51,720
FORGET TO SUBMIT YOUR

1761
01:26:51,720 --> 01:26:52,200
QUESTIONS FOR THE PANEL

1762
01:26:52,200 --> 01:26:52,680
DISCUSSION COMING UP.

1763
01:26:52,680 --> 01:26:57,640
THE FINAL SPEAKER SESSION ONE

1764
01:26:57,640 --> 01:26:58,040
WE WILL TALK ABOUT

1765
01:26:58,040 --> 01:27:01,720
OPPORTUNITIES AND CHALLENGES

1766
01:27:01,720 --> 01:27:03,320
FOR MEDICINES BASED ON

1767
01:27:03,320 --> 01:27:07,080
BACTERIAL CONSORTIUM.

1768
01:27:07,080 --> 01:27:12,840
>> THANK YOU VERY MUCH.

1769
01:27:12,840 --> 01:27:22,120
DR. MENON: THANK YOU VERY MUCH

1770
01:27:22,120 --> 01:27:22,680
FOR THE OPPORTUNITY TO SPEAK

1771
01:27:22,680 --> 01:27:23,280
HERE TODAY AND TO THE REST OF

1772
01:27:23,280 --> 01:27:24,360
THE SPEAKERS FOR THEIR

1773
01:27:24,360 --> 01:27:26,320
EXCELLENT INSIGHTS AND

1774
01:27:26,320 --> 01:27:26,880
RESEARCH PRESENTED SO FAR.

1775
01:27:26,880 --> 01:27:28,840
THE ASPECT OF PRECISION ARE

1776
01:27:28,840 --> 01:27:33,120
THE CHALLENGES HAS TO DO WITH

1777
01:27:33,120 --> 01:27:36,480
ONCE THE DRUG MEASURES

1778
01:27:36,480 --> 01:27:37,880
AFFECTED WHAT IS NEEDED TO

1779
01:27:37,880 --> 01:27:40,360
RATIONALIZE CHEMICAL SUCCESS

1780
01:27:40,360 --> 01:27:44,280
AND FEARS AND THEN A SHARE OF

1781
01:27:44,280 --> 01:27:46,680
THOSE STUDIES OF CONSORTIA.

1782
01:27:46,680 --> 01:27:50,240
I AM AN EMPLOYEE AND WHAT WE

1783
01:27:50,240 --> 01:27:56,320
SHARE TODAY'S BASED ON

1784
01:27:56,320 --> 01:27:56,920
ANYTHING THAT HAS NOT BEEN YET

1785
01:27:56,920 --> 01:27:58,840
APPROVED BY THE FDA BACK

1786
01:27:58,840 --> 01:28:02,920
TESTED.

1787
01:28:02,920 --> 01:28:07,480
>> TO MAKE AN ANALOGY THAT HAS

1788
01:28:07,480 --> 01:28:12,080
BEEN RAPIDLY ADVANCING SOME OF

1789
01:28:12,080 --> 01:28:15,360
THOSE BIOLOGICS AND THAT

1790
01:28:15,360 --> 01:28:17,800
EVOLUTION OVER THE PAST

1791
01:28:17,800 --> 01:28:21,520
CENTURY AND THOSE CHALLENGES

1792
01:28:21,520 --> 01:28:23,760
IN THE MICROBIOTA AND IN

1793
01:28:23,760 --> 01:28:26,640
ESSENCE SOLVING A SIMILAR

1794
01:28:26,640 --> 01:28:30,760
PROBLEM THE COMPLEX BIOLOGICAL

1795
01:28:30,760 --> 01:28:32,920
MATERIAL IS DIFFICULT TO

1796
01:28:32,920 --> 01:28:38,960
QUANTIFY THAT POPULATION IN

1797
01:28:38,960 --> 01:28:42,600
THE CONTEXT OF PLASMA AND

1798
01:28:42,600 --> 01:28:47,520
FINALLY THEN WITH ACTIVE

1799
01:28:47,520 --> 01:28:48,320
INGREDIENTS WITH THE

1800
01:28:48,320 --> 01:28:52,720
UNDERSTANDING OF THE FACTORS

1801
01:28:52,720 --> 01:28:57,520
DEFINED CONSORTIA TO PRECISELY

1802
01:28:57,520 --> 01:28:58,840
SCREEN AND CHARACTERIZE AND

1803
01:28:58,840 --> 01:29:03,520
MANUFACTURE AND TRACK THE DRUG

1804
01:29:03,520 --> 01:29:04,680
AND AMONG OTHER THINGS IT LETS

1805
01:29:04,680 --> 01:29:15,720
US ASK TARGETED QUESTIONS THAT

1806
01:29:15,720 --> 01:29:17,560
WE DO NEED TO ESTABLISH SOME

1807
01:29:17,560 --> 01:29:19,520
DEFINITIONS OF THE BIO

1808
01:29:19,520 --> 01:29:22,280
THERAPEUTIC PRODUCT.

1809
01:29:22,280 --> 01:29:27,920
HOW THE HOST AFFECTS THE DRUG

1810
01:29:27,920 --> 01:29:28,400
CAN BE THOUGHT OF OF THE

1811
01:29:28,400 --> 01:29:29,480
ABUNDANCE OF THE BACTERIA AND

1812
01:29:29,480 --> 01:29:31,640
THE AFFECTION AND HOW LONG

1813
01:29:31,640 --> 01:29:33,160
THEY STICK AROUND FOR SO THE

1814
01:29:33,160 --> 01:29:37,040
PERSISTENCE AND THAT HAS TO DO

1815
01:29:37,040 --> 01:29:39,040
WITH HOW THE DRUG AFFECTS THIS

1816
01:29:39,040 --> 01:29:44,400
IS ABOUT BIOCHEMICAL AND FOR

1817
01:29:44,400 --> 01:29:45,360
MICROBIOTA TREATMENTS IT HAS

1818
01:29:45,360 --> 01:29:49,080
TO INCLUDE THE MICROBIOTA AND

1819
01:29:49,080 --> 01:29:51,560
METABOLITES.

1820
01:29:51,560 --> 01:29:55,600
IT'S VERY DIFFICULT TO CAPTURE

1821
01:29:55,600 --> 01:29:57,440
THE REASONABLE QUANTITATIVE

1822
01:29:57,440 --> 01:30:04,560
WAYS IN THESE PROCEDURES

1823
01:30:04,560 --> 01:30:05,960
BECAUSE OF THE BATCH TO BATCH

1824
01:30:05,960 --> 01:30:06,560
VARIABILITY AND MAKES IT HARD

1825
01:30:06,560 --> 01:30:06,920
TO RATIONALIZE.

1826
01:30:06,920 --> 01:30:11,120
IT'S CHALLENGING EVEN IN THE

1827
01:30:11,120 --> 01:30:16,280
CONTEXT BUT IT IS FEASIBLE.

1828
01:30:16,280 --> 01:30:17,240
SO WHAT DO I MEAN ABOUT

1829
01:30:17,240 --> 01:30:22,520
COMPLEXITY WITH THE HUMAN

1830
01:30:22,520 --> 01:30:28,200
DEFENSE OF THE TRIFECTA AND

1831
01:30:28,200 --> 01:30:32,320
THE BIOCHEMICAL HABITAT AND

1832
01:30:32,320 --> 01:30:34,920
THE DISEASE CONTEXT AND SO ON.

1833
01:30:34,920 --> 01:30:36,560
SOME OF THE FACTORS I HAVE

1834
01:30:36,560 --> 01:30:40,240
HIGHLIGHTED THE IMPACT OF THE

1835
01:30:40,240 --> 01:30:46,440
DOSING SCHEDULE AND

1836
01:30:46,440 --> 01:30:48,120
IMPORTANTLY THE INTERACTION

1837
01:30:48,120 --> 01:30:48,600
WITH THE BROAD-SPECTRUM

1838
01:30:48,600 --> 01:30:52,360
ANTIBIOTICS AND WITH NO OTHER

1839
01:30:52,360 --> 01:30:55,280
BACTERIAL DEFEND CITY MINE --

1840
01:30:55,280 --> 01:30:58,840
DENSITY AND THEN TO CREATE A

1841
01:30:58,840 --> 01:31:01,520
CHANGE FOR ADVANCEMENT.

1842
01:31:01,520 --> 01:31:09,240
SO THE FOCUS OF MY TALK TODAY

1843
01:31:09,240 --> 01:31:09,840
WILL ADDRESS AS WHAT I VIEW AS

1844
01:31:09,840 --> 01:31:10,440
A KEY GAP IN THE CLINICALS ON

1845
01:31:10,440 --> 01:31:13,080
-- THE CLINICAL SPACE

1846
01:31:13,080 --> 01:31:17,800
PARTICULARLY WITH RESPECT WITH

1847
01:31:17,800 --> 01:31:22,920
ANTIBIOTICS.

1848
01:31:22,920 --> 01:31:24,480
BUT BEFORE WE GET THERE WITH

1849
01:31:24,480 --> 01:31:25,000
THE ISSUE OF DRAFTING THE

1850
01:31:25,000 --> 01:31:25,520
BACTERIA THAT HAVE BEEN

1851
01:31:25,520 --> 01:31:26,480
INTRODUCED AND TELLING THEM

1852
01:31:26,480 --> 01:31:28,720
APART FROM WHAT WAS ALREADY

1853
01:31:28,720 --> 01:31:29,240
THERE.

1854
01:31:29,240 --> 01:31:31,480
OUR APPROACHES SOLVING THIS

1855
01:31:31,480 --> 01:31:34,760
PROBLEM HAS TWO STEPS PUSHING

1856
01:31:34,760 --> 01:31:41,920
THAT UNIQUE SO ON THOSE

1857
01:31:41,920 --> 01:31:44,720
GENOMES AND THEN WE HAVE A

1858
01:31:44,720 --> 01:31:49,200
PROCESS IN EACH GENOME THAT IS

1859
01:31:49,200 --> 01:31:52,680
BASED ON COVERAGE ONE IS SHOWN

1860
01:31:52,680 --> 01:31:56,920
ON THE X AND THE OTHER THAT IS

1861
01:31:56,920 --> 01:31:58,840
THE INVESTIGATIONAL PRODUCT

1862
01:31:58,840 --> 01:32:01,640
AND EVERYTHING IN GREEN

1863
01:32:01,640 --> 01:32:03,280
REPRESENTS EXPECTED

1864
01:32:03,280 --> 01:32:08,040
RELATIONSHIP FROM THE META-

1865
01:32:08,040 --> 01:32:09,160
GENOMIC SAMPLE AND THOSE

1866
01:32:09,160 --> 01:32:10,960
DEVIATIONS IN RED FOR EXAMPLE

1867
01:32:10,960 --> 01:32:13,480
CAN INDICATE A HIGH DEPTH OR

1868
01:32:13,480 --> 01:32:17,320
PART OF THE GENOME THIS CAN BE

1869
01:32:17,320 --> 01:32:22,840
AN ARTIFACT AND WITH THIS

1870
01:32:22,840 --> 01:32:30,920
APPROACH AND THEN LOOKING AT

1871
01:32:30,920 --> 01:32:37,760
THOSE KINETICS.

1872
01:32:37,760 --> 01:32:42,840
AND THEN WITH THOSE

1873
01:32:42,840 --> 01:32:44,960
MODALITIES.

1874
01:32:44,960 --> 01:32:48,240
AND WITH THOSE LONG-DISTANCE

1875
01:32:48,240 --> 01:32:48,440
CASE.

1876
01:32:48,440 --> 01:32:50,000
AND THEN PLEASE STICK AROUND

1877
01:32:50,000 --> 01:32:53,120
TO UP TO A YEAR.

1878
01:32:53,120 --> 01:32:58,720
AND THESE QUANTITIES THE

1879
01:32:58,720 --> 01:33:07,000
OVERALL EXPOSURE AND ARE THEY

1880
01:33:07,000 --> 01:33:08,080
DOSE-DEPENDENT?

1881
01:33:08,080 --> 01:33:13,160
AND IF THE TREND EXIST IS THAT

1882
01:33:13,160 --> 01:33:14,200
PART OF THE CONSORTIUM THAT

1883
01:33:14,200 --> 01:33:14,800
NOW WE ARE STARTING TO COLLECT

1884
01:33:14,800 --> 01:33:24,760
THE DATA TO ANSWER THESE TYPES

1885
01:33:24,760 --> 01:33:25,320
OF QUESTIONS AND THIS IS A

1886
01:33:25,320 --> 01:33:25,800
SIDE THAT MAKES ME VERY

1887
01:33:25,800 --> 01:33:26,000
HAPPY.

1888
01:33:26,000 --> 01:33:27,040
THESE ARE STOOL SAMPLES

1889
01:33:27,040 --> 01:33:30,200
COLLECTED THROUGH PHASE I AND

1890
01:33:30,200 --> 01:33:30,800
PHASE II STUDIES IN DIFFERENT

1891
01:33:30,800 --> 01:33:36,720
PATIENT POPULATIONS.

1892
01:33:36,720 --> 01:33:37,760
AND WITH THOSE SAMPLE

1893
01:33:37,760 --> 01:33:38,360
COLLECTIONS DURING ANTIBIOTIC

1894
01:33:38,360 --> 01:33:46,040
TREATMENT AND DOSING.

1895
01:33:46,040 --> 01:33:49,520
AND OF THE HOST BIOME SYSTEM

1896
01:33:49,520 --> 01:33:52,200
WITHIN THE FRAMEWORK.

1897
01:33:52,200 --> 01:33:55,640
AND OF THOSE FEATURES MAY BE

1898
01:33:55,640 --> 01:33:58,640
GENERALIZED AND I WILL GIVE

1899
01:33:58,640 --> 01:34:05,080
YOU A COUPLE OF EXAMPLES AND

1900
01:34:05,080 --> 01:34:14,640
THEN THOSE VOLUNTEERS AND THAT

1901
01:34:14,640 --> 01:34:15,120
WAS RECENTLY PUBLISHED A

1902
01:34:15,120 --> 01:34:18,280
COUPLE OF WEEKS AGO AND THE

1903
01:34:18,280 --> 01:34:24,440
DETAILS GO CHECK IT OUT.

1904
01:34:24,440 --> 01:34:26,960
AND THEN WITH THOSE

1905
01:34:26,960 --> 01:34:31,720
FREQUENCIES.

1906
01:34:31,720 --> 01:34:32,920
AND THEN TO CONTROL THE ONLY

1907
01:34:32,920 --> 01:34:38,120
ONE THERE WAS AN ANTIBIOTIC

1908
01:34:38,120 --> 01:34:44,320
AND THEN SO THEN WE LOOKED AT

1909
01:34:44,320 --> 01:34:55,640
WHAT GOD IN.

1910
01:34:55,640 --> 01:34:56,720
AND THEN ON THE AXIS FROM THE

1911
01:34:56,720 --> 01:35:01,760
START OF DOSING FROM ONE YEAR

1912
01:35:01,760 --> 01:35:07,920
AFTER AND SO THOSE HIGH LEVELS

1913
01:35:07,920 --> 01:35:08,360
OF OBSERVATIONS CAN BE

1914
01:35:08,360 --> 01:35:12,600
DISTINGUISHED IN THE GROUP

1915
01:35:12,600 --> 01:35:17,440
WHICH IS ONE OF THOSE COHORTS

1916
01:35:17,440 --> 01:35:17,960
AND WE SEE THOSE SPECIFIC

1917
01:35:17,960 --> 01:35:20,920
DETECTIONS IS VERY DIFFERENT

1918
01:35:20,920 --> 01:35:24,000
FROM VERY MORE QUANTIFIABLE

1919
01:35:24,000 --> 01:35:26,520
WERE THIS IS MOSTLY

1920
01:35:26,520 --> 01:35:30,760
BACKGROUND.

1921
01:35:30,760 --> 01:35:35,040
AND THOSE ARE DETECTED IN MOST

1922
01:35:35,040 --> 01:35:39,080
REGIMENS AND THERE IS A

1923
01:35:39,080 --> 01:35:40,520
DISTINCT DOSE FROM SINGLE-DOSE

1924
01:35:40,520 --> 01:35:43,920
CORE FOR COHORTS HERE YOU CAN

1925
01:35:43,920 --> 01:35:45,920
SEE AN INCREASE THAT IS MORE

1926
01:35:45,920 --> 01:35:50,920
ROBUST AND FINALLY AND THEN

1927
01:35:50,920 --> 01:35:55,160
ENHANCES COLONIZATION AND THAT

1928
01:35:55,160 --> 01:35:57,280
HAS MUCH MORE COLONIZATION

1929
01:35:57,280 --> 01:36:05,120
FROM THESE COHORTS SO LOOKING

1930
01:36:05,120 --> 01:36:11,400
AT ABUNDANCE THAT YOU CAN SEE

1931
01:36:11,400 --> 01:36:15,120
EXPANDING THE ABUNDANCE AND

1932
01:36:15,120 --> 01:36:16,840
THAT WE REACH LEVELS THAT ARE

1933
01:36:16,840 --> 01:36:20,320
COMPARABLE BETWEEN ONE AND

1934
01:36:20,320 --> 01:36:22,880
10 PERCENT AND THEN THROUGHOUT

1935
01:36:22,880 --> 01:36:25,680
WEEK 12 AND STARTS TO DEFINE

1936
01:36:25,680 --> 01:36:30,000
AFTERWORDS AND IN TRADITION

1937
01:36:30,000 --> 01:36:32,520
USING TO QUANTIFY THAT

1938
01:36:32,520 --> 01:36:35,160
EXPOSURE OR TO GO BACK TO

1939
01:36:35,160 --> 01:36:38,600
CONSORTIUM THEN TO CALCULATE

1940
01:36:38,600 --> 01:36:44,240
THE AREA AND THEN WE CAN

1941
01:36:44,240 --> 01:36:48,720
CONSOLIDATE WOULD'VE TOLD HER

1942
01:36:48,720 --> 01:36:54,680
ON -- TOTAL EXPOSURE WITH THE

1943
01:36:54,680 --> 01:37:02,920
SINGLE INCREASING DOSES.

1944
01:37:02,920 --> 01:37:04,120
AND THEN TO EXPOSE THE TREND

1945
01:37:04,120 --> 01:37:15,160
IS EVIDENT AND WE CAN SEE THAT

1946
01:37:15,160 --> 01:37:19,120
AND THEN IT IS NECESSARY AT A

1947
01:37:19,120 --> 01:37:20,120
HIGH LEVEL FOR A LONGER PERIOD

1948
01:37:20,120 --> 01:37:29,000
OF TIME SPENT THESE

1949
01:37:29,000 --> 01:37:29,560
OBSERVATIONS ARE GENERALIZED

1950
01:37:29,560 --> 01:37:30,120
AGAINST THE CONSORTIA AND

1951
01:37:30,120 --> 01:37:31,680
LARGER STUDIES WITH THIS

1952
01:37:31,680 --> 01:37:36,040
EXPOSURE TO THE DOSE.

1953
01:37:36,040 --> 01:37:39,240
WITH THOSE COMBINATIONS WITH A

1954
01:37:39,240 --> 01:37:47,440
HIGH DOSE LEVEL AND THEN THIS

1955
01:37:47,440 --> 01:37:50,920
CONFIRMS THOSE OBSERVATIONS SO

1956
01:37:50,920 --> 01:37:54,760
FIRST IN THE LEFT COLUMN

1957
01:37:54,760 --> 01:37:56,280
NEITHER COHORTS SEIZED

1958
01:37:56,280 --> 01:38:00,120
COLONIZATION BUT IN THE MULTI-

1959
01:38:00,120 --> 01:38:03,520
DAY DOSING WE SEE THE

1960
01:38:03,520 --> 01:38:08,520
TRANSIENT COLONIZATION IT

1961
01:38:08,520 --> 01:38:09,520
DECLINES AFTER ACTIVE DOSING

1962
01:38:09,520 --> 01:38:14,520
IS COMPLETED.

1963
01:38:14,520 --> 01:38:16,920
WHERE AS IN THE RIGHTMOST

1964
01:38:16,920 --> 01:38:18,680
COLUMN YOU SEE CONDITIONING

1965
01:38:18,680 --> 01:38:23,120
ROBUST COLONIZATION AFTER SIX

1966
01:38:23,120 --> 01:38:27,520
MONTHS AND THE HIGH DOSE GROUP

1967
01:38:27,520 --> 01:38:31,720
BUT IT IS HIGHER.

1968
01:38:31,720 --> 01:38:35,000
SO THEN ON A SINGLE SLIDE, WE

1969
01:38:35,000 --> 01:38:38,720
SEE THE FINDING IT IS

1970
01:38:38,720 --> 01:38:41,280
IMPORTANT THROUGH THE

1971
01:38:41,280 --> 01:38:50,080
CONSORTIA WHILE THE DOSE LEVEL

1972
01:38:50,080 --> 01:38:50,920
HAS A LESSER AND LESS

1973
01:38:50,920 --> 01:39:02,440
CONSISTENT EFFECT.

1974
01:39:02,440 --> 01:39:03,480
AND THEN TO GET STRINGS INTO

1975
01:39:03,480 --> 01:39:06,440
THE SUBJECT AND THEN EIGHT

1976
01:39:06,440 --> 01:39:09,120
WEEKS AFTER STARTING DOSES OF

1977
01:39:09,120 --> 01:39:16,680
HOW LONG IT TAKES.

1978
01:39:16,680 --> 01:39:18,000
>> BUT BEFORE I WIND UP I WANT

1979
01:39:18,000 --> 01:39:20,040
TO GIVE YOU A BRIEF TASTE OF

1980
01:39:20,040 --> 01:39:27,960
THE COMPLEXITY.

1981
01:39:27,960 --> 01:39:30,520
BECAUSE THE DOSE AND THE

1982
01:39:30,520 --> 01:39:34,720
MICROBIOTA.

1983
01:39:34,720 --> 01:39:40,080
SO THAT TOP LEFT THIS IS THE

1984
01:39:40,080 --> 01:39:42,960
MEASURE ONCE AGAIN FROM LEFT

1985
01:39:42,960 --> 01:39:49,560
TO RIGHT AND THAT IS WHERE IT

1986
01:39:49,560 --> 01:39:56,920
STARTED OUT AND ONE WEEK AFTER.

1987
01:39:56,920 --> 01:40:00,080
BUT THE DIFFERENCE FROM LEFT

1988
01:40:00,080 --> 01:40:02,840
TO RIGHT INDICATES

1989
01:40:02,840 --> 01:40:05,440
DOSE-DEPENDENT RECOVERY SO

1990
01:40:05,440 --> 01:40:08,600
QUICKER IN A HIGHER DOSE

1991
01:40:08,600 --> 01:40:11,520
GROUPS.

1992
01:40:11,520 --> 01:40:14,080
AND WHILE THIS IS HAPPENING A

1993
01:40:14,080 --> 01:40:23,080
DIMINISHING OF FACTS.

1994
01:40:23,080 --> 01:40:25,720
AND IN THOSE COHORTS AND THE

1995
01:40:25,720 --> 01:40:30,960
OTHER MEASURE OF RECOVERY.

1996
01:40:30,960 --> 01:40:32,000
AND IM SHOWING ON THE LEFT

1997
01:40:32,000 --> 01:40:33,760
WITH THE PRIMARY AND SECONDARY

1998
01:40:33,760 --> 01:40:37,920
THAT ARE ELEVATED IN THE STATE

1999
01:40:37,920 --> 01:40:41,720
WITH SPECIFIC THEY ARE KNOWN

2000
01:40:41,720 --> 01:40:44,240
TO INSTIGATE WHERE THE

2001
01:40:44,240 --> 01:40:48,040
SECONDARY ARE SUPPRESSED OR

2002
01:40:48,040 --> 01:40:49,160
INHIBITS FORMATION AND THAT IS

2003
01:40:49,160 --> 01:40:50,280
WHY IT IS CLINICALLY RELEVANT

2004
01:40:50,280 --> 01:40:52,680
IF WE LOOK AT IT FROM THE

2005
01:40:52,680 --> 01:41:00,440
APPLICATION.

2006
01:41:00,440 --> 01:41:01,560
AND THOSE ASSETS ON THE LEFT

2007
01:41:01,560 --> 01:41:07,320
AND THE EXPEDITED RECOVERY AND

2008
01:41:07,320 --> 01:41:08,600
IN FACT THE CONVERSION PRIMARY

2009
01:41:08,600 --> 01:41:14,000
TO SECONDARY THE GET COMMUNITY

2010
01:41:14,000 --> 01:41:15,040
STARTS OF THE GROUPS OF

2011
01:41:15,040 --> 01:41:20,720
MICROBIOTA AND AND WITH THOSE

2012
01:41:20,720 --> 01:41:23,000
THERAPEUTICS IT HAS TO BE TIED

2013
01:41:23,000 --> 01:41:28,320
TO THE MICROBIOLOGY.

2014
01:41:28,320 --> 01:41:31,000
>> AND JUST WHAT I HAVE'S

2015
01:41:31,000 --> 01:41:38,400
SHOWN YOU TODAY THAT IS A LOT

2016
01:41:38,400 --> 01:41:39,200
OF ACRONYMS BUT IT IS CRITICAL

2017
01:41:39,200 --> 01:41:43,840
TO MAKE SENSE AND STEP ONE TO

2018
01:41:43,840 --> 01:41:45,920
FIGURE OUT WHY A STUDY WORKED

2019
01:41:45,920 --> 01:41:56,120
AND WHY IT DID NOT AND WITH

2020
01:41:56,120 --> 01:41:56,720
THOSE GENOMICS AND THE LIBRARY

2021
01:41:56,720 --> 01:41:57,320
COULD BE USED TO TELL APART

2022
01:41:57,320 --> 01:41:59,320
THE STRAINS INTRODUCED FROM

2023
01:41:59,320 --> 01:42:00,440
THOSE THAT ARE ALREADY IN

2024
01:42:00,440 --> 01:42:04,240
PEOPLE THAT KEEP IN MIND THAT

2025
01:42:04,240 --> 01:42:07,920
I MEASURE OVERALL DRUG

2026
01:42:07,920 --> 01:42:10,120
EXPOSURE THAT MAKES US DRUG

2027
01:42:10,120 --> 01:42:10,720
DEPENDENT.

2028
01:42:10,720 --> 01:42:14,720
AND THEN THE MICROBIOTA WITH

2029
01:42:14,720 --> 01:42:16,800
THOSE DEPENDENT AFFECTS SEEN

2030
01:42:16,800 --> 01:42:25,440
IN THE RECOVERY.

2031
01:42:25,440 --> 01:42:26,040
AND WITH THAT I WOULD JUST

2032
01:42:26,040 --> 01:42:29,880
LIKE TO ACKNOWLEDGE THE VERY

2033
01:42:29,880 --> 01:42:35,560
TALENTED TEAM FROM JANSSEN

2034
01:42:35,560 --> 01:42:41,280
PHARMACEUTICALS AND OUR KEY

2035
01:42:41,280 --> 01:42:41,800
COLLABORATORS THAT ALLOWED

2036
01:42:41,800 --> 01:42:42,320
THIS MAMMOTH WORK TO COME

2037
01:42:42,320 --> 01:42:42,600
TOGETHER.

2038
01:42:42,600 --> 01:42:43,720
THANK YOU VERY MUCH FOR YOUR

2039
01:42:43,720 --> 01:42:44,160
ATTENTION.

2040
01:42:44,160 --> 01:42:49,280
>> THANK YOU LIKE THAT

2041
01:42:49,280 --> 01:42:53,720
MECHANISTIC MICROBIAL.

2042
01:42:53,720 --> 01:42:55,200
THAT'S A TERM OF THE DAY SO

2043
01:42:55,200 --> 01:42:55,720
FOR THE PANEL DISCUSSION I

2044
01:42:55,720 --> 01:43:00,520
WILL TURN THAT OVER TO START

2045
01:43:00,520 --> 01:43:12,360
THE DISCUSSION WITH GABRIELLA.

2046
01:43:12,360 --> 01:43:14,840
>> THANK YOU FOR THE WONDERFUL

2047
01:43:14,840 --> 01:43:18,760
SPEAKERS AND IN MANY

2048
01:43:18,760 --> 01:43:25,480
CHALLENGES WITH DISCUSSION AND

2049
01:43:25,480 --> 01:43:27,960
WE HOPE WE CAN GO MORE IN

2050
01:43:27,960 --> 01:43:30,880
DEPTH TO SOME OF THE

2051
01:43:30,880 --> 01:43:32,560
CHALLENGES.

2052
01:43:32,560 --> 01:43:48,320
THAT THE INVESTIGATORS AND SO

2053
01:43:48,320 --> 01:43:57,280
THEN ACTUALLY SO WE HAVE THOSE

2054
01:43:57,280 --> 01:44:01,680
QUESTIONS AND THEN ASK IF HE

2055
01:44:01,680 --> 01:44:03,960
CAN ADDRESS WHAT ARE THE

2056
01:44:03,960 --> 01:44:06,920
CLINICAL GAPS FOR THE

2057
01:44:06,920 --> 01:44:14,440
KNOWLEDGE AND METHODOLOGY?

2058
01:44:14,440 --> 01:44:16,920
AND WHAT ARE THE NEW

2059
01:44:16,920 --> 01:44:19,040
RESOURCES?

2060
01:44:19,040 --> 01:44:21,080
AND THEN TO ADDRESS SOME OF

2061
01:44:21,080 --> 01:44:28,400
THE GAPS.

2062
01:44:28,400 --> 01:44:35,240
>> IT IS A VERY LONG QUESTION.

2063
01:44:35,240 --> 01:44:40,480
I WILL ALSO DEFER TO OTHERS.

2064
01:44:40,480 --> 01:44:41,320
THERE IS A LOT.

2065
01:44:41,320 --> 01:44:41,880
AS A SAID IN MY TALK WE HAVE

2066
01:44:41,880 --> 01:44:44,760
TO REMEMBER HOW BIG THE FIELD

2067
01:44:44,760 --> 01:44:48,720
THIS IS.

2068
01:44:48,720 --> 01:44:49,240
AND THEN WITH THE BENCH

2069
01:44:49,240 --> 01:44:49,920
RESEARCH AND HOW FAR WE HAVE

2070
01:44:49,920 --> 01:44:51,320
COME.

2071
01:44:51,320 --> 01:44:52,600
ALSO WE NEED TO REMEMBER HOW

2072
01:44:52,600 --> 01:45:00,920
FAR WE ARE FOR THOSE THAT HAVE

2073
01:45:00,920 --> 01:45:01,440
LESS DIET AND MICROBIOTA

2074
01:45:01,440 --> 01:45:07,280
INFLUENCE.

2075
01:45:07,280 --> 01:45:08,960
BUT WE HAVE LOTS OF EXCITING

2076
01:45:08,960 --> 01:45:09,520
THINGS THAT WILL HAPPEN OVER

2077
01:45:09,520 --> 01:45:13,800
THE NEXT 20 YEARS.

2078
01:45:13,800 --> 01:45:18,960
>> BUT CLINICALLY THE MOST

2079
01:45:18,960 --> 01:45:20,120
EXCITING IS WHAT JEFF IS

2080
01:45:20,120 --> 01:45:20,440
TALKING ABOUT.

2081
01:45:20,440 --> 01:45:26,840
AND OBVIOUSLY AND THAT IS

2082
01:45:26,840 --> 01:45:27,760
WHERE A LOT OF RESEARCH WILL

2083
01:45:27,760 --> 01:45:32,000
GO.

2084
01:45:32,000 --> 01:45:36,320
I DON'T THINK IT IS A CURE-ALL

2085
01:45:36,320 --> 01:45:39,800
AND THEN WITH DIABETES AND

2086
01:45:39,800 --> 01:45:48,920
HYPER TRIGLYCERIDES BUT.

2087
01:45:48,920 --> 01:45:51,400
>> BUT I HAVE ONE SPECIFIC

2088
01:45:51,400 --> 01:46:04,120
QUESTION.

2089
01:46:04,120 --> 01:46:12,520
AND THEN AND THEN HAD WE MAKE

2090
01:46:12,520 --> 01:46:19,840
IT WORK?

2091
01:46:19,840 --> 01:46:20,880
AND THEN WITH A COMPLIANCE FOR

2092
01:46:20,880 --> 01:46:22,360
THE DIET OR THE DATA

2093
01:46:22,360 --> 01:46:25,640
COLLECTION.

2094
01:46:25,640 --> 01:46:27,960
AND WITH THOSE CLINICAL

2095
01:46:27,960 --> 01:46:30,920
TRIALS.

2096
01:46:30,920 --> 01:46:32,160
AND THEN DAYS SEND OR

2097
01:46:32,160 --> 01:46:32,760
SOMETHING AND THEN WE COLLECT

2098
01:46:32,760 --> 01:46:34,560
THE PILLS AT THE END BUT THE

2099
01:46:34,560 --> 01:46:38,640
NICE THING IS YOU CAN TEST

2100
01:46:38,640 --> 01:46:39,120
WITH THE INTERVENTION

2101
01:46:39,120 --> 01:46:39,360
PROBABLY.

2102
01:46:39,360 --> 01:46:43,680
YOU CANNOT BE SURE BUT

2103
01:46:43,680 --> 01:46:47,800
COMPLIANCE AGAIN CLINICAL

2104
01:46:47,800 --> 01:46:48,240
MEDICINE IS SLOPPY.

2105
01:46:48,240 --> 01:46:54,880
IT'S PROBABLY HARDER EVEN IN

2106
01:46:54,880 --> 01:46:56,320
BETHESDA MARYLAND PATIENTS ARE

2107
01:46:56,320 --> 01:47:01,040
NOT ALWAYS IN COMPLIANCE SO WE

2108
01:47:01,040 --> 01:47:02,120
ALWAYS TRIED TO MEASURE AND

2109
01:47:02,120 --> 01:47:08,400
THEN THE SECOND PART I FORGOT.

2110
01:47:08,400 --> 01:47:10,760
>> IT IS THE EXPRESSION WHY

2111
01:47:10,760 --> 01:47:16,440
DID IT WORK?

2112
01:47:16,440 --> 01:47:19,640
SO THOSE THINGS TO PUT BACK

2113
01:47:19,640 --> 01:47:26,760
AND THEN TO SPECIALIZE IT'S AN

2114
01:47:26,760 --> 01:47:27,320
IMPORTANT OBSERVATION WE CAN

2115
01:47:27,320 --> 01:47:27,520
MAKE.

2116
01:47:27,520 --> 01:47:29,800
BECAUSE IT WORKED OR DID NOT

2117
01:47:29,800 --> 01:47:37,960
WORK.

2118
01:47:37,960 --> 01:47:38,960
AND THEN TO LESSEN SOMETHING

2119
01:47:38,960 --> 01:47:43,200
LIKE THAT.

2120
01:47:43,200 --> 01:47:43,720
WITH THAT EXPERIENCE WITH

2121
01:47:43,720 --> 01:47:49,800
SOMETHING TO SHARE.

2122
01:47:49,800 --> 01:47:50,320
>> THESE ARE 10000-FOOT

2123
01:47:50,320 --> 01:47:50,560
QUESTIONS.

2124
01:47:50,560 --> 01:47:50,840
[LAUGHTER]

2125
01:47:50,840 --> 01:47:57,760
>> I KNOW.

2126
01:47:57,760 --> 01:48:01,920
>> I AM WONDERING IF I CAN

2127
01:48:01,920 --> 01:48:02,480
THROW A QUESTION OUT THERE?

2128
01:48:02,480 --> 01:48:06,240
I AM WONDERING FOR OTHER

2129
01:48:06,240 --> 01:48:07,800
MEMBERS AND OTHER SPEAKERS IN

2130
01:48:07,800 --> 01:48:13,280
THE FIRST SESSION ARE THERE

2131
01:48:13,280 --> 01:48:14,160
APPROACHES THAT CAN BE ADOPTED

2132
01:48:14,160 --> 01:48:15,440
FOR INTERVENTIONS FROM GENETIC

2133
01:48:15,440 --> 01:48:16,680
RESEARCH WHERE PEOPLE ARE

2134
01:48:16,680 --> 01:48:20,760
RANDOMIZED ACCORDING TO A

2135
01:48:20,760 --> 01:48:22,920
RELEVANT GENOTYPE LIKE OMEGA-3

2136
01:48:22,920 --> 01:48:24,960
FATTY ACID SYNTHESIS ON

2137
01:48:24,960 --> 01:48:30,240
POLYMORPHISM TYPE ARE THERE

2138
01:48:30,240 --> 01:48:31,800
METHODS FOR OTHER INTEGRATED

2139
01:48:31,800 --> 01:48:33,680
MODALITIES WITH MEDICAL

2140
01:48:33,680 --> 01:48:35,280
APPROACHES OFTEN WITH

2141
01:48:35,280 --> 01:48:41,280
DIFFERENT PARTICIPANTS HAVE A

2142
01:48:41,280 --> 01:48:41,880
RANDOMIZED STRUCTURED APPROACH

2143
01:48:41,880 --> 01:48:42,400
TO DIFFERENT INTERVENTIONS

2144
01:48:42,400 --> 01:48:45,600
BASED ON THE CHARACTERISTICS

2145
01:48:45,600 --> 01:48:46,200
AT THE START OF THE TRIAL ARE

2146
01:48:46,200 --> 01:48:49,120
SOME OF THOSE APPROACHES

2147
01:48:49,120 --> 01:48:55,200
USEFUL FOR STUDYING PROBIOTICS

2148
01:48:55,200 --> 01:49:00,440
BASED ON DIET AND

2149
01:49:00,440 --> 01:49:03,080
CHARACTERISTICS HOW DO YOU GO

2150
01:49:03,080 --> 01:49:07,880
ABOUT USING THAT INSTRUCTION

2151
01:49:07,880 --> 01:49:08,080
QUICK.

2152
01:49:08,080 --> 01:49:09,080
>> I THANK YOU ARE ASKING AN

2153
01:49:09,080 --> 01:49:12,120
AWFUL LOT.

2154
01:49:12,120 --> 01:49:14,680
THAT'S A WONDERFUL QUESTION

2155
01:49:14,680 --> 01:49:16,040
BUT MICROBIAL COMMUNITY IN

2156
01:49:16,040 --> 01:49:19,960
DIFFERENT COMPONENTS ARE MANY

2157
01:49:19,960 --> 01:49:22,360
DIFFERENT THINGS TO HOST

2158
01:49:22,360 --> 01:49:25,200
BIOLOGY AND THOSE WOULD HAVE

2159
01:49:25,200 --> 01:49:27,400
DIFFERENT EFFECT SIZES AND

2160
01:49:27,400 --> 01:49:34,000
THEN YOU HAVE TO BEGIN BY THE

2161
01:49:34,000 --> 01:49:34,480
GIFT OF ATTENTION ONE

2162
01:49:34,480 --> 01:49:35,040
BIOLOGICAL QUESTION IN TERMS

2163
01:49:35,040 --> 01:49:35,600
OF THE RELATIONSHIP BETWEEN

2164
01:49:35,600 --> 01:49:40,640
MICROBIAL COMMUNITY AND THE

2165
01:49:40,640 --> 01:49:44,800
OPERATIONS.

2166
01:49:44,800 --> 01:49:49,560
AND THE TYPE OF STEPS THAT THE

2167
01:49:49,560 --> 01:49:51,120
SPEAKER TALKS ABOUT HER HIGHLY

2168
01:49:51,120 --> 01:49:57,880
RELEVANT AND TO DEFINE A

2169
01:49:57,880 --> 01:49:58,320
PARTICULAR TARGET TO

2170
01:49:58,320 --> 01:49:58,840
UNDERSTAND THE BIOLOGICAL

2171
01:49:58,840 --> 01:50:00,160
SIGNIFICANCE OF STRING LEVEL

2172
01:50:00,160 --> 01:50:03,120
VARIATION WHICH IS ENORMOUSLY

2173
01:50:03,120 --> 01:50:09,720
INSPIRING.

2174
01:50:09,720 --> 01:50:10,320
IF YOU DO IDENTIFY THE TARGETS

2175
01:50:10,320 --> 01:50:10,840
OF THE PRECLINICAL MODELS

2176
01:50:10,840 --> 01:50:11,440
REPRESENTATIVE OF A POPULATION

2177
01:50:11,440 --> 01:50:15,280
AS A WHOLE, STILL TASK WITH

2178
01:50:15,280 --> 01:50:17,720
THE EXPERIMENTAL MEDICINE

2179
01:50:17,720 --> 01:50:19,920
PARADIGM OF RANDOMIZED

2180
01:50:19,920 --> 01:50:28,600
CONTROLLED STUDY TO UNDERSTAND

2181
01:50:28,600 --> 01:50:29,160
WHAT THE INDIVIDUAL IS PRIOR

2182
01:50:29,160 --> 01:50:29,760
TO THE INTERVENTION IF YOU HIT

2183
01:50:29,760 --> 01:50:30,080
THE TARGET.

2184
01:50:30,080 --> 01:50:30,640
AND THEN THE EFFECT SIZE OF

2185
01:50:30,640 --> 01:50:31,720
THE POPULATION.

2186
01:50:31,720 --> 01:50:34,120
THAT WILL BE THE PREREQUISITE

2187
01:50:34,120 --> 01:50:45,080
FOR SUBSEQUENT TRIALS.

2188
01:50:45,080 --> 01:50:46,120
IF YOU DO SEE THAT EFFECT ON A

2189
01:50:46,120 --> 01:50:47,640
HOST SYSTEM THEN YOU HAVE TO

2190
01:50:47,640 --> 01:50:53,920
DETERMINE IF THAT INTERVENTION

2191
01:50:53,920 --> 01:50:54,440
IS A DIRECT RESULT OF THE

2192
01:50:54,440 --> 01:50:55,040
ORGANISM OF INTEREST AND IF IT

2193
01:50:55,040 --> 01:50:57,120
IS PRODUCING EFFECT VOICE

2194
01:50:57,120 --> 01:50:59,520
INTERACTION WITH OTHER

2195
01:50:59,520 --> 01:51:02,640
ELEMENTS.

2196
01:51:02,640 --> 01:51:04,520
AND THIS IS WHAT THE FIELD IS

2197
01:51:04,520 --> 01:51:06,040
ABOUT.

2198
01:51:06,040 --> 01:51:08,080
AND DIFFERENT COMPONENTS OF

2199
01:51:08,080 --> 01:51:10,160
DIFFERENT MICROBIAL

2200
01:51:10,160 --> 01:51:13,320
COMMUNITIES.

2201
01:51:13,320 --> 01:51:22,520
AND SO I'M WORRIED THIS IS

2202
01:51:22,520 --> 01:51:26,520
ABOUT SYSTEMS BIOLOGY SO THAT

2203
01:51:26,520 --> 01:51:34,120
IS MY PHILOSOPHICAL RESPONSE.

2204
01:51:34,120 --> 01:51:47,600
>> SO IS THIS A SYSTEM BIOLOGY

2205
01:51:47,600 --> 01:51:57,120
AND MICROBIOLOGY.

2206
01:51:57,120 --> 01:51:58,120
>> ONE ASPECT OF EXPERIMENTAL

2207
01:51:58,120 --> 01:51:59,360
MEDICINE JUST ONE TEAM

2208
01:51:59,360 --> 01:52:05,200
APPROACHING ALL DISEASES?

2209
01:52:05,200 --> 01:52:05,800
THE QUESTION ASKING ABOUT

2210
01:52:05,800 --> 01:52:06,360
COMPLEXITY AND BRAIN BIOLOGY

2211
01:52:06,360 --> 01:52:08,320
OF NEURODEVELOPMENT THERE IS

2212
01:52:08,320 --> 01:52:10,720
SO MANY DIMENSIONS TO THAT AND

2213
01:52:10,720 --> 01:52:13,640
SO MANY ASKED ABOUT THOSE IN

2214
01:52:13,640 --> 01:52:21,920
THE MICROBIOTA.

2215
01:52:21,920 --> 01:52:31,760
>> I JUST WANT TO ADD THE

2216
01:52:31,760 --> 01:52:32,320
FOLLOWING THAT WE UNDERSTAND

2217
01:52:32,320 --> 01:52:32,920
THE COMPLEXITY OF THE ACTIONS

2218
01:52:32,920 --> 01:52:35,160
OF THE SYSTEM TO BRING

2219
01:52:35,160 --> 01:52:38,680
RESOURCES AND DATABASES TO

2220
01:52:38,680 --> 01:52:43,000
MOVE FORWARD.

2221
01:52:43,000 --> 01:52:46,240
BUT THAT IS THE PRODUCTS OF

2222
01:52:46,240 --> 01:52:55,160
THE BACTERIA AND THEN TALK

2223
01:52:55,160 --> 01:52:59,560
ABOUT THOSE COMPOUNDS.

2224
01:52:59,560 --> 01:53:02,120
AND THAT IS CORRELATED WITH

2225
01:53:02,120 --> 01:53:03,960
ANXIETY.

2226
01:53:03,960 --> 01:53:07,160
AND THESE ARE MARKERS TO MOVE

2227
01:53:07,160 --> 01:53:12,120
FROM THIS COMPLEXITY.

2228
01:53:12,120 --> 01:53:13,960
AND THEN WE CAN MESH ON --

2229
01:53:13,960 --> 01:53:17,400
MEASURE AND METABOLIZE.

2230
01:53:17,400 --> 01:53:32,400
AND WITH THE STRATIFICATION

2231
01:53:32,400 --> 01:53:33,000
AND LOOK AT THOSE WHO ARE THE

2232
01:53:33,000 --> 01:53:33,520
MOST AFFLICTED WITH THAT

2233
01:53:33,520 --> 01:53:38,280
CHANGE OF THE MICROBIOTA SO

2234
01:53:38,280 --> 01:53:41,760
I'M SAYING THAT BIOCHEMISTRY

2235
01:53:41,760 --> 01:53:43,320
CAN EVEN MARK THAT

2236
01:53:43,320 --> 01:53:45,560
STRATIFICATION IF WE DON'T

2237
01:53:45,560 --> 01:53:46,160
UNDERSTAND THAT COMPLEXITY OF

2238
01:53:46,160 --> 01:53:52,080
THE INTERACTIONS TO SATISFY AM

2239
01:53:52,080 --> 01:53:57,640
UP FOR A RESPONSE.

2240
01:53:57,640 --> 01:54:00,120
SO IS THAT CORRELATED WITH THE

2241
01:54:00,120 --> 01:54:00,600
BENEFIT?

2242
01:54:00,600 --> 01:54:04,280
WE DO HAVE THE PROMISE WHILE

2243
01:54:04,280 --> 01:54:08,120
WE LOOK AT THE COMPLEXITY.

2244
01:54:08,120 --> 01:54:14,520
>> .

2245
01:54:14,520 --> 01:54:18,840
>> THANK YOU I JUST WANT TO

2246
01:54:18,840 --> 01:54:21,480
ECHO THAT THE TRIAL IS

2247
01:54:21,480 --> 01:54:26,720
DEPENDENT ON THE QUESTION.

2248
01:54:26,720 --> 01:54:32,320
SO DO YOU THINK IN THE SPACE

2249
01:54:32,320 --> 01:54:38,920
WITH THAT ADAPTIVE TRIAL FOR

2250
01:54:38,920 --> 01:54:41,680
STUDY POPULATIONS.

2251
01:54:41,680 --> 01:54:47,360
AND ALSO IT HAS A LARGE

2252
01:54:47,360 --> 01:54:52,520
PLACEBO THAT'S UNANTICIPATED

2253
01:54:52,520 --> 01:54:53,640
THAT'S ALLOW YOU TO GROW YOUR

2254
01:54:53,640 --> 01:54:56,800
SAMPLE SIZE.

2255
01:54:56,800 --> 01:54:57,360
SO THESE ARE TECHNIQUES THAT

2256
01:54:57,360 --> 01:55:12,720
CAN BE USED EITHER TO IDENTIFY

2257
01:55:12,720 --> 01:55:14,000
AND THEN IT IS A TOOL THAT CAN

2258
01:55:14,000 --> 01:55:21,240
BE USED.

2259
01:55:21,240 --> 01:55:24,360
>> THE QUESTION HAS TO BE WELL

2260
01:55:24,360 --> 01:55:36,720
THOUGHT OF AND PRECISE.

2261
01:55:36,720 --> 01:55:45,120
>> AND THAT IS VERY SPOT ON

2262
01:55:45,120 --> 01:55:49,760
AND THERE IS A NEED WITH NON-

2263
01:55:49,760 --> 01:56:02,000
MICROBIOTA AND THEN AND HOW TO

2264
01:56:02,000 --> 01:56:04,400
DO PATIENT ELECTION AND

2265
01:56:04,400 --> 01:56:12,120
STRATIFICATION.

2266
01:56:12,120 --> 01:56:13,120
AND THEN TO HAVE THAT

2267
01:56:13,120 --> 01:56:19,720
ECOLOGICAL OUTCOME AND THEN IF

2268
01:56:19,720 --> 01:56:21,040
YOU ARE TRYING TO MODULATE THE

2269
01:56:21,040 --> 01:56:22,080
ACCESS OR STIMULATE THE IMMUNE

2270
01:56:22,080 --> 01:56:23,880
SYSTEM.

2271
01:56:23,880 --> 01:56:24,960
YOU MAY HAVE VERY DIFFERENT

2272
01:56:24,960 --> 01:56:27,280
WAYS THE COMMUNITY RESPONSE

2273
01:56:27,280 --> 01:56:28,400
AND THE WAY YOU MIGHT THINK

2274
01:56:28,400 --> 01:56:31,360
ABOUT IDENTIFYING PATIENTS WHO

2275
01:56:31,360 --> 01:56:32,960
ARE MOST LIKELY TO BENEFIT

2276
01:56:32,960 --> 01:56:35,720
FROM THAT KIND OF INTERVENTION.

2277
01:56:35,720 --> 01:56:37,080
SO IT'S IMPORTANT WE ARE

2278
01:56:37,080 --> 01:56:39,680
STARTING TO DO THIS NOW TO

2279
01:56:39,680 --> 01:56:42,520
DEFINE THE DATA THAT IS NEEDED

2280
01:56:42,520 --> 01:56:47,000
THAT CAN THEN BE USED IN THE

2281
01:56:47,000 --> 01:56:52,360
SYNDICATIONS AND CATEGORIES SO

2282
01:56:52,360 --> 01:56:53,720
HOW DO WE SELECT A PATIENT AND

2283
01:56:53,720 --> 01:56:55,920
WHY IT IS THE SIGNATURE?

2284
01:56:55,920 --> 01:56:59,520
IT SIMPLER WHEN WE TRY TO SEE

2285
01:56:59,520 --> 01:57:01,720
ECOLOGICALLY WHAT TYPE OF

2286
01:57:01,720 --> 01:57:04,200
MATHEMATICAL METHODS THAT CAN

2287
01:57:04,200 --> 01:57:08,400
BE PREDICTED BASED ON THAT BUT

2288
01:57:08,400 --> 01:57:11,920
IT BECOMES MUCH HARDER WITH

2289
01:57:11,920 --> 01:57:18,040
THOSE RESPONSES.

2290
01:57:18,040 --> 01:57:22,360
AND THEN WE NEED DATA TO PUT

2291
01:57:22,360 --> 01:57:25,880
THE PRINCIPLES OF PRECISION

2292
01:57:25,880 --> 01:57:27,400
INTO A FIELD THAT IS HARD TO

2293
01:57:27,400 --> 01:57:34,920
GENERALIZ GENERALIZE.

2294
01:57:34,920 --> 01:57:43,600
>> IT'S THE SAME TYPE OF DATA.

2295
01:57:43,600 --> 01:57:47,200
>> I JUST WANT TO EXTEND THE

2296
01:57:47,200 --> 01:57:53,480
COMMENT BUT PHARMA STILL

2297
01:57:53,480 --> 01:57:54,080
STRUGGLES TO IDENTIFY PATIENT

2298
01:57:54,080 --> 01:57:54,600
POPULATIONS THAT ARE MOST

2299
01:57:54,600 --> 01:57:57,600
LIKELY TO RESPOND TO DISEASES

2300
01:57:57,600 --> 01:58:00,120
THAT HAS BEEN DRUGGED FOR

2301
01:58:00,120 --> 01:58:01,800
DECADES.

2302
01:58:01,800 --> 01:58:07,280
AND THE HOST OF OTHERS AND

2303
01:58:07,280 --> 01:58:10,920
IT'S VERY HARD TO KNOW WITH

2304
01:58:10,920 --> 01:58:13,520
THOSE THAT ARE CLINICAL

2305
01:58:13,520 --> 01:58:13,760
TRIALS.

2306
01:58:13,760 --> 01:58:19,040
TO UNDERSTAND IS THAT FOR THE

2307
01:58:19,040 --> 01:58:22,080
FIELD OF THE MICROBIOTA VERY

2308
01:58:22,080 --> 01:58:26,280
COMPLEX TO A PARTICULAR

2309
01:58:26,280 --> 01:58:29,120
DISORDER THAT IS BEEN FIGURED

2310
01:58:29,120 --> 01:58:32,680
OUT.

2311
01:58:32,680 --> 01:58:35,280
SO WE STILL NEED MORE DATA.

2312
01:58:35,280 --> 01:58:38,880
AND WITH THOSE GENETIC

2313
01:58:38,880 --> 01:58:41,040
DISORDERS COULD CONSTRAIN AND

2314
01:58:41,040 --> 01:58:43,360
INCREASE THE PART BUT WE'RE

2315
01:58:43,360 --> 01:58:49,160
NOT THERE YET FOR MICROBIOTA.

2316
01:58:49,160 --> 01:58:53,000
SO WE SELECT FOR CRITERIA IS

2317
01:58:53,000 --> 01:58:55,520
THAT HAD GASTROINTESTINAL

2318
01:58:55,520 --> 01:59:01,720
SYMPTOMS AND THEN THAT ARE

2319
01:59:01,720 --> 01:59:03,320
FUNDAMENTALLY ARE SECONDARILY

2320
01:59:03,320 --> 01:59:05,920
RELATED AND THAT HYPOTHESIS IN

2321
01:59:05,920 --> 01:59:06,520
THE FIELD OF CLINICAL TRIAL WE

2322
01:59:06,520 --> 01:59:12,840
DON'T KNOW.

2323
01:59:12,840 --> 01:59:13,320
AND OF THOSE PARTICULAR

2324
01:59:13,320 --> 01:59:24,640
VARIABLES SIDE-BY-SIDE.

2325
01:59:24,640 --> 01:59:25,120
>> BUT BECAUSE AS ACTIVE

2326
01:59:25,120 --> 01:59:38,720
RESPONSE OF ALL SITUATIONS IN

2327
01:59:38,720 --> 01:59:38,920
THAT.

2328
01:59:38,920 --> 01:59:41,240
>> THE MICROBIOTA IS NOT

2329
01:59:41,240 --> 01:59:43,760
EVERYTHING.

2330
01:59:43,760 --> 01:59:46,280
AND WITH THE ELECTRONIC HEALTH

2331
01:59:46,280 --> 01:59:52,360
RECORDS AND THEN TO HARMONIZE

2332
01:59:52,360 --> 01:59:52,880
AND THOSE TRUE FEATURES

2333
01:59:52,880 --> 01:59:56,520
PATIENCE TO RESPOND THOSE ARE

2334
01:59:56,520 --> 02:00:00,840
MICROBIOLOGICAL AND IN YOU AND

2335
02:00:00,840 --> 02:00:02,040
RELATED TO DEMOGRAPHIC DATA

2336
02:00:02,040 --> 02:00:08,920
FOR EXAMPLE.

2337
02:00:08,920 --> 02:00:09,360
AND JUST EXPECTING THE

2338
02:00:09,360 --> 02:00:09,920
MICROBIOTA AND WHO WOULD BE

2339
02:00:09,920 --> 02:00:14,760
RESPONSIVE TO TREATMENT.

2340
02:00:14,760 --> 02:00:15,320
WE NEED TO TAKE A FAR MORE

2341
02:00:15,320 --> 02:00:21,120
HOLISTIC VIEW OF HUMAN BIOLOGY

2342
02:00:21,120 --> 02:00:24,880
AND THOSE OF THOSE

2343
02:00:24,880 --> 02:00:32,160
INTERACTIONS.

2344
02:00:32,160 --> 02:00:40,480
>> .

2345
02:00:40,480 --> 02:00:41,840
>> AND THOSE STRATEGIES THAT

2346
02:00:41,840 --> 02:00:42,320
ARE INTERESTING BUT ONLY

2347
02:00:42,320 --> 02:00:47,120
USEFUL CLINICALLY AND THEN TO

2348
02:00:47,120 --> 02:00:53,960
BE VALIDATED.

2349
02:00:53,960 --> 02:00:59,040
AND HOW LONG WOULD THAT TAKE?

2350
02:00:59,040 --> 02:01:09,200
>> I CAN COMMENT.

2351
02:01:09,200 --> 02:01:15,120
SO THEN TO IDENTIFY CERTAINLY

2352
02:01:15,120 --> 02:01:16,720
WILL HELP US AND FOCUS

2353
02:01:16,720 --> 02:01:25,760
STRATEGIES SO WITH THOSE

2354
02:01:25,760 --> 02:01:26,440
COMPOUNDS.

2355
02:01:26,440 --> 02:01:27,720
AND THEN WE ARE WITHIN THOSE

2356
02:01:27,720 --> 02:01:30,320
COMPOUNDS WITH A HANDFUL OF

2357
02:01:30,320 --> 02:01:34,760
THOSE METABOLITES.

2358
02:01:34,760 --> 02:01:37,320
AND WITH THAT TARGETED

2359
02:01:37,320 --> 02:01:41,120
APPROACH SO THAN THE

2360
02:01:41,120 --> 02:01:46,440
FEASIBILITY AND THAT IS

2361
02:01:46,440 --> 02:01:52,320
DEFINITELY DOABLE.

2362
02:01:52,320 --> 02:01:54,880
>> IF THEY WANT TO COMMENT ON

2363
02:01:54,880 --> 02:02:04,960
THIS?

2364
02:02:04,960 --> 02:02:10,400
>> SO THE PART ABOUT FEATURE

2365
02:02:10,400 --> 02:02:11,520
SELECTION IS THE OTHER

2366
02:02:11,520 --> 02:02:13,520
CHALLENGES OF COURSE IF YOU DO

2367
02:02:13,520 --> 02:02:20,480
AND INTERVENTION OF WHATEVER

2368
02:02:20,480 --> 02:02:29,400
INTERVENTION AND THAT IS A

2369
02:02:29,400 --> 02:02:35,240
DEMANDING SET OF CHALLENGES.

2370
02:02:35,240 --> 02:02:38,040
AND WITH THAT CAPACITY TO DO

2371
02:02:38,040 --> 02:02:38,600
LONGITUDINAL STUDY ON --

2372
02:02:38,600 --> 02:02:41,040
LONGITUDINAL STUDIES.

2373
02:02:41,040 --> 02:02:41,760
AND THOSE EFFECTS COULD BE

2374
02:02:41,760 --> 02:02:44,920
QUITE PROFOUND.

2375
02:02:44,920 --> 02:02:53,120
AND THEN TO DETERMINE.

2376
02:02:53,120 --> 02:02:57,240
>> SO THE NEXT QUESTION IS IT

2377
02:02:57,240 --> 02:03:01,360
IS INCREASINGLY CLEAR THAT IN

2378
02:03:01,360 --> 02:03:03,880
THE MICROBIOTA TO AFFECT THAT

2379
02:03:03,880 --> 02:03:04,920
POSITION?

2380
02:03:04,920 --> 02:03:07,400
HOW IS THAT I'M TAKING INTO

2381
02:03:07,400 --> 02:03:14,800
ACCOUNT THE SAMPLE COLLECTION

2382
02:03:14,800 --> 02:03:15,320
AND IT IS IMPOSSIBLE FOR

2383
02:03:15,320 --> 02:03:15,920
RENOVATIONS TAKEN INTERVENTION

2384
02:03:15,920 --> 02:03:18,920
OR IS IT EASIER TO NOTICE THAT

2385
02:03:18,920 --> 02:03:21,920
TIME OF THE SAMPLE COLLECTION?

2386
02:03:21,920 --> 02:03:29,520
AND I WILL ADD ONE MORE THING.

2387
02:03:29,520 --> 02:03:35,520
AND THAT IS PART OF THE

2388
02:03:35,520 --> 02:03:45,280
TRANSLATION.

2389
02:03:45,280 --> 02:03:47,800
>> THANK YOU FOR ASKING THE

2390
02:03:47,800 --> 02:03:49,120
QUESTION.

2391
02:03:49,120 --> 02:03:49,920
WE CAN TALK ABOUT THAT A

2392
02:03:49,920 --> 02:03:51,520
LITTLE BIT LATER THIS

2393
02:03:51,520 --> 02:03:54,920
AFTERNOON.

2394
02:03:54,920 --> 02:03:57,320
SO WHERE LOOKING AT A MOVIE

2395
02:03:57,320 --> 02:04:03,120
WERE TRYING TO TAKE A SNAPSHOT

2396
02:04:03,120 --> 02:04:11,440
SO IN A NORMAL CHILD DIET SO

2397
02:04:11,440 --> 02:04:12,720
IS DIFFERENT THAN DURING THE

2398
02:04:12,720 --> 02:04:13,960
DAY WE ARE STARTING TO SEE

2399
02:04:13,960 --> 02:04:18,560
EVIDENCE THOSE MICROBIOTA

2400
02:04:18,560 --> 02:04:23,040
SAMPLES.

2401
02:04:23,040 --> 02:04:25,560
AND THAT JUST SHOWS WHAT

2402
02:04:25,560 --> 02:04:27,080
OCCURS IS JUST A PARENT IF YOU

2403
02:04:27,080 --> 02:04:29,480
LOOK AT LARGE POPULATIONS.

2404
02:04:29,480 --> 02:04:32,120
WE HAVE BEEN LOOKING AT IT

2405
02:04:32,120 --> 02:04:35,600
WITH THE LARGE CIRCADIAN

2406
02:04:35,600 --> 02:04:37,720
CHALLENGES AS WELL AS SEASONAL

2407
02:04:37,720 --> 02:04:47,560
CHANGES IN THE MICROBIOTA.

2408
02:04:47,560 --> 02:04:51,400
SO THE RULES THIS IS WHAT

2409
02:04:51,400 --> 02:05:00,120
WE'RE TRYING TO UNDERSTAND.

2410
02:05:00,120 --> 02:05:01,200
AND THEN MAY NOT TRANSLATE TO

2411
02:05:01,200 --> 02:05:02,680
HUMANS THAT CLEARLY BECAUSE

2412
02:05:02,680 --> 02:05:05,760
USUALLY WHEN PEOPLE SAMPLE

2413
02:05:05,760 --> 02:05:06,320
FROM MICE THEY ARE SAMPLING

2414
02:05:06,320 --> 02:05:12,200
DURING THE DAY WHICH MICE ARE

2415
02:05:12,200 --> 02:05:13,280
NOCTURNAL SO THEY ARE NORMALLY

2416
02:05:13,280 --> 02:05:13,760
EATING HAVE A DIFFERENT

2417
02:05:13,760 --> 02:05:15,640
MICROBIOTA DURING THE NIGHT.

2418
02:05:15,640 --> 02:05:18,120
SO WE NEED TO BE STUDYING THAT

2419
02:05:18,120 --> 02:05:25,720
MORE IN THE NIGHTTIME.

2420
02:05:25,720 --> 02:05:26,320
AND THAT BETTER CORRESPONDS TO

2421
02:05:26,320 --> 02:05:26,880
HUMANS DURING THE DAY BUT WE

2422
02:05:26,880 --> 02:05:29,080
NEED TO UNDERSTAND THE

2423
02:05:29,080 --> 02:05:34,400
IMPLICATION TO UNDERSTAND IF

2424
02:05:34,400 --> 02:05:35,480
THAT IS WHY SOME OF THE

2425
02:05:35,480 --> 02:05:38,960
CHANGES OF THE MICE DON'T

2426
02:05:38,960 --> 02:05:40,320
TRANSLATE INTO HUMANS OR IF WE

2427
02:05:40,320 --> 02:05:41,520
CAN CREATE MORE EFFECTIVE

2428
02:05:41,520 --> 02:05:48,120
MICROBIOTA MEDIA THERAPY.

2429
02:05:48,120 --> 02:05:54,120
>> .

2430
02:05:54,120 --> 02:06:10,640
>> SO THEN TO FAIL.

2431
02:06:10,640 --> 02:06:13,360
BUT THEN THE ONE THING THAT IS

2432
02:06:13,360 --> 02:06:19,920
A POTENTIAL SOLUTION, CAN YOU

2433
02:06:19,920 --> 02:06:22,920
SHARE YOUR SOURCE AROUND THE

2434
02:06:22,920 --> 02:06:26,040
TRIAL AND HOW YOU ARE WORKING

2435
02:06:26,040 --> 02:06:29,880
TO THAT PRECISION?

2436
02:06:29,880 --> 02:06:36,560
>> .

2437
02:06:36,560 --> 02:06:40,040
>> .

2438
02:06:40,040 --> 02:06:42,560
>> AND IS GENERALLY A

2439
02:06:42,560 --> 02:06:45,160
CROSSOVER.

2440
02:06:45,160 --> 02:06:47,720
WHAT THEY ARE GETTING AND THE

2441
02:06:47,720 --> 02:06:52,520
RESEARCH.

2442
02:06:52,520 --> 02:06:53,840
AND THAT IS.02 PERCENT OF

2443
02:06:53,840 --> 02:06:56,760
CLINICAL TRIALS.

2444
02:06:56,760 --> 02:06:58,320
AND THEY ARE DIFFICULT AND

2445
02:06:58,320 --> 02:07:03,640
TIME-CONSUMING AND THERE ARE

2446
02:07:03,640 --> 02:07:04,920
SOME OF THOSE STUDIES BUT I

2447
02:07:04,920 --> 02:07:05,720
THINK IT'S POSSIBLE BUT I

2448
02:07:05,720 --> 02:07:11,640
DON'T THINK IT'S THE ANSWER

2449
02:07:11,640 --> 02:07:14,200
AND THEN IT CAUSED A LOT OF

2450
02:07:14,200 --> 02:07:18,440
RESOURCES.

2451
02:07:18,440 --> 02:07:22,280
>> FOR THE SECOND QUESTION.

2452
02:07:22,280 --> 02:07:27,520
SO THROUGH TRANSLATION WE ARE

2453
02:07:27,520 --> 02:07:39,440
HERE TO TOUCH ON THAT SO HOW

2454
02:07:39,440 --> 02:07:51,960
OFTEN BUT MANY OF THESE GROUPS

2455
02:07:51,960 --> 02:07:56,320
SO IF WE ARE THINKING ABOUT

2456
02:07:56,320 --> 02:07:58,920
RESEARCH FROM THE CLINICAL

2457
02:07:58,920 --> 02:08:07,760
TRIAL.

2458
02:08:07,760 --> 02:08:08,520
AND THEN FOR THE NEXT PAPER

2459
02:08:08,520 --> 02:08:19,960
TRIAL FOR PRECISION?

2460
02:08:19,960 --> 02:08:33,000
>> AND I WORK A LOT WITH NIAID

2461
02:08:33,000 --> 02:08:33,600
AND WITH THEIR CLINICAL TRIALS

2462
02:08:33,600 --> 02:08:34,160
WITH ASTHMA AND ALLERGY AND

2463
02:08:34,160 --> 02:08:34,720
THE MECHANISTIC STUDIES WITH

2464
02:08:34,720 --> 02:08:35,320
THE OLDER CLINICAL TRIALS TO

2465
02:08:35,320 --> 02:08:43,720
PROVIDE FUNDING SO THAT WE CAN

2466
02:08:43,720 --> 02:08:44,320
MAXIMIZE OUR UNDERSTANDING OF

2467
02:08:44,320 --> 02:08:44,720
HOW TREATMENTS AND

2468
02:08:44,720 --> 02:08:45,160
INTERVENTIONS FROM THE

2469
02:08:45,160 --> 02:08:45,720
MICROBIOLOGICAL AND IMMUNE

2470
02:08:45,720 --> 02:08:46,000
PERSPECTIVE.

2471
02:08:46,000 --> 02:08:46,640
AND THAT IS JUST AN INCREDIBLE

2472
02:08:46,640 --> 02:08:47,520
INFRASTRUCTURE TO HAVE IN

2473
02:08:47,520 --> 02:08:52,960
PLACE AND THEN TO MAXIMIZE THE

2474
02:08:52,960 --> 02:08:55,280
UNDERSTANDING OF HUMAN

2475
02:08:55,280 --> 02:09:04,720
EXPERIMENTS AND WITH THAT

2476
02:09:04,720 --> 02:09:06,000
INFRASTRUCTURE TO UNDERSTAND

2477
02:09:06,000 --> 02:09:06,440
THAT BIOLOGICAL AND

2478
02:09:06,440 --> 02:09:11,440
MECHANISTIC INTERVENTION OF

2479
02:09:11,440 --> 02:09:14,600
POPULATIONS.

2480
02:09:14,600 --> 02:09:17,120
AND THAT'S AN INCREDIBLE

2481
02:09:17,120 --> 02:09:20,120
RESOURCE.

2482
02:09:20,120 --> 02:09:26,720
WITH ALLERGY AND ASTHMA.

2483
02:09:26,720 --> 02:09:37,320
>> .

2484
02:09:37,320 --> 02:09:43,800
>> AND THEN YOU CAN TELL WHAT

2485
02:09:43,800 --> 02:09:48,320
IT WAS AND YOU CAN SET AN

2486
02:09:48,320 --> 02:09:51,520
EXAMPLE DO YOU NEED A STREAM

2487
02:09:51,520 --> 02:09:52,760
TO BE THERE FOR A LONG PERIOD

2488
02:09:52,760 --> 02:10:00,760
OF TIME SO IS IT ENOUGH TO

2489
02:10:00,760 --> 02:10:01,360
HAVE A LOW ABUNDANT STREAM IN

2490
02:10:01,360 --> 02:10:03,400
THE BACKGROUND OR SOME OTHER

2491
02:10:03,400 --> 02:10:12,600
ASPECT?

2492
02:10:12,600 --> 02:10:15,120
AND THEN THINKING

2493
02:10:15,120 --> 02:10:19,200
SPECIFICALLY.

2494
02:10:19,200 --> 02:10:23,960
BUT WHAT WOULD BE REALLY BAD

2495
02:10:23,960 --> 02:10:27,320
AND BASED ON THE OBSERVATIONS

2496
02:10:27,320 --> 02:10:29,120
FOR A RESPONSE OF A PARTICULAR

2497
02:10:29,120 --> 02:10:36,320
INDICATION AND WITH TIMING AND

2498
02:10:36,320 --> 02:10:43,240
EXTENT OF CHANGES THE ECOLOGY

2499
02:10:43,240 --> 02:10:44,560
AND THEN FOR HOW LONG CERTAIN

2500
02:10:44,560 --> 02:10:45,920
STREAMS NEED TO BE PRESENT AND

2501
02:10:45,920 --> 02:10:48,320
THEN ANOTHER THING THAT IS

2502
02:10:48,320 --> 02:10:54,600
POSSIBLE IS USE THE CLINICAL

2503
02:10:54,600 --> 02:10:56,240
EXCESSES FROM PEOPLE THAT

2504
02:10:56,240 --> 02:10:56,680
RESPOND BETTER TO AN

2505
02:10:56,680 --> 02:11:01,680
INTERVENTION AND THEN TO SEE

2506
02:11:01,680 --> 02:11:07,320
YOU NEXT GENERATION DRUGS WITH

2507
02:11:07,320 --> 02:11:08,280
THAT ITERATIVE OPTIMIZATION OF

2508
02:11:08,280 --> 02:11:19,200
THE MONTH AND THEN BIT BY BIT

2509
02:11:19,200 --> 02:11:21,040
SO THE MORE YOU START TO

2510
02:11:21,040 --> 02:11:25,280
MEASURE THAT IS A SUCCESS OF

2511
02:11:25,280 --> 02:11:27,640
CLINICAL TRIALS BACK INTO THE

2512
02:11:27,640 --> 02:11:29,760
LAB AND THEN TO MEASURE WHAT

2513
02:11:29,760 --> 02:11:31,840
WAS DIFFERENT AND THAT IS A

2514
02:11:31,840 --> 02:11:33,600
KEY PIECE MISSING FROM THE

2515
02:11:33,600 --> 02:11:45,720
FORWARD TRANSLATION AND WITH

2516
02:11:45,720 --> 02:11:47,120
THOSE VARIABLES OF THE HUMAN

2517
02:11:47,120 --> 02:11:53,040
POPULATIONS AND THEN WITH THE

2518
02:11:53,040 --> 02:11:54,160
OPPORTUNITY TO RATIONALIZE

2519
02:11:54,160 --> 02:12:02,720
THEM BACKWARDS.

2520
02:12:02,720 --> 02:12:14,120
>> SOMEBODY WANT TO COMMENT?

2521
02:12:14,120 --> 02:12:18,200
>> .

2522
02:12:18,200 --> 02:12:25,680
>> I WANT TO MAKE THE POINT

2523
02:12:25,680 --> 02:12:26,640
AND THEN THE ADVANCE

2524
02:12:26,640 --> 02:12:28,840
UNDERSTANDING THE TO FOLLOW UP

2525
02:12:28,840 --> 02:12:31,760
ON THE NEXT GENERATION.

2526
02:12:31,760 --> 02:12:38,240
AND THEN THEN IF WE EXPERIENCE

2527
02:12:38,240 --> 02:12:39,320
TO BE VERY ATTENTIVE TO

2528
02:12:39,320 --> 02:12:42,200
INFORMED CONSENT AND THEN TO

2529
02:12:42,200 --> 02:12:47,320
BE THOUGHTFUL ABOUT THAT WITH

2530
02:12:47,320 --> 02:12:49,920
OF THE ANTI- GUN CULTURE

2531
02:12:49,920 --> 02:12:50,440
COMMUNITIES AND THEN THOSE

2532
02:12:50,440 --> 02:12:53,400
ORGANISMS.

2533
02:12:53,400 --> 02:12:55,920
AND THEN THE LAST PIECE ABOUT

2534
02:12:55,920 --> 02:13:01,040
IT AT THE TIME THAT THEY ARE

2535
02:13:01,040 --> 02:13:03,640
PRODUCED.

2536
02:13:03,640 --> 02:13:07,680
AND ALL OF THIS REQUIRES THE

2537
02:13:07,680 --> 02:13:11,480
PERSON THAT JUST SPOKE OF

2538
02:13:11,480 --> 02:13:13,960
ADVANCED THINKING OF

2539
02:13:13,960 --> 02:13:15,520
ORGANIZATION.

2540
02:13:15,520 --> 02:13:19,840
THAT IS AN INSTRUMENTAL PART

2541
02:13:19,840 --> 02:13:22,360
OF EXPERIMENTAL MEDICINE FOR

2542
02:13:22,360 --> 02:13:24,480
TRANSLATION.

2543
02:13:24,480 --> 02:13:26,080
DOES THAT PLAY INTO YOUR

2544
02:13:26,080 --> 02:13:26,280
PLANS.

2545
02:13:26,280 --> 02:13:27,120
THANK YOU.

2546
02:13:27,120 --> 02:13:38,560
>> .

2547
02:13:38,560 --> 02:13:39,120
>> I JUST WANT TO GO BACK TO

2548
02:13:39,120 --> 02:13:45,280
THE CONCEPT OF AN F1 BUT WITH

2549
02:13:45,280 --> 02:13:47,520
THAT STUDY BUT ACE ENORMOUS

2550
02:13:47,520 --> 02:13:49,840
POWER FOR TO LOOK AT THE

2551
02:13:49,840 --> 02:13:56,440
INDIVIDUAL AND THEN TO HAVE

2552
02:13:56,440 --> 02:13:58,600
THE GENOME.

2553
02:13:58,600 --> 02:14:08,360
AND IT IS EXTREMELY POWERFUL.

2554
02:14:08,360 --> 02:14:09,000
AND THEN WITH THE COMMUNITY OF

2555
02:14:09,000 --> 02:14:17,160
METABOLIC RESEARCHERS.

2556
02:14:17,160 --> 02:14:21,800
AND THOSE BECAUSE EVERY DEFECT

2557
02:14:21,800 --> 02:14:27,320
IN METABOLISM.

2558
02:14:27,320 --> 02:14:29,320
THAT HAS MADE A HUGE IMPACT

2559
02:14:29,320 --> 02:14:34,920
WITH THE TREATMENT OF CANCER.

2560
02:14:34,920 --> 02:14:39,240
AND THOSE IT HAS BECOME.

2561
02:14:39,240 --> 02:14:41,720
AND THEN TO BE GROUPED

2562
02:14:41,720 --> 02:14:46,720
TOGETHER AND THEN FROM THE

2563
02:14:46,720 --> 02:14:57,160
DATE DATA THAT IS GATHERED.

2564
02:14:57,160 --> 02:15:02,080
>> .

2565
02:15:02,080 --> 02:15:04,440
>> I JUST WANT TO GIVE MY

2566
02:15:04,440 --> 02:15:04,680
SUPPORT.

2567
02:15:04,680 --> 02:15:08,600
FOR THE MISSED OPPORTUNITY

2568
02:15:08,600 --> 02:15:15,880
FROM THE RESEARCH WITH THAT

2569
02:15:15,880 --> 02:15:16,880
CHARACTERIZATION ALL THE WAY

2570
02:15:16,880 --> 02:15:19,520
THROUGH CLINICAL TRIALS AND

2571
02:15:19,520 --> 02:15:22,040
THAT INFORMATION BACK FROM THE

2572
02:15:22,040 --> 02:15:29,840
CLINIC AND THEN TO COLLECT

2573
02:15:29,840 --> 02:15:31,960
THAT DATA.

2574
02:15:31,960 --> 02:15:33,560
AND THEN TO TRANSLATE.

2575
02:15:33,560 --> 02:15:36,120
SO THE VALUE DOESN'T GET

2576
02:15:36,120 --> 02:15:38,600
LOCKED INTO A SINGLE ONE SO

2577
02:15:38,600 --> 02:15:45,080
HAVING A COMMON PLATFORM THAT

2578
02:15:45,080 --> 02:15:52,200
IS A CRITICAL PIECE TO THAT.

2579
02:15:52,200 --> 02:16:02,840
>> INDEED YES.

2580
02:16:02,840 --> 02:16:05,480
AND THEN TO MOVE TO THE NEXT

2581
02:16:05,480 --> 02:16:12,360
QUESTION SO WHAT IS THE

2582
02:16:12,360 --> 02:16:16,520
BIOAVAILABILITY?

2583
02:16:16,520 --> 02:16:17,840
SO HOW IS THIS ASSESSED?

2584
02:16:17,840 --> 02:16:24,440
CAN IT BE ASSESSED?

2585
02:16:24,440 --> 02:16:29,280
AND THEN WHAT ABOUT THE GAP?

2586
02:16:29,280 --> 02:16:32,600
>> I CAN COMMENT ON THIS SINCE

2587
02:16:32,600 --> 02:16:38,920
I WAS ON THIS TOPIC BUT USING

2588
02:16:38,920 --> 02:16:39,520
MEASURES OF EXPOSURE THAT ARE

2589
02:16:39,520 --> 02:16:41,360
ECOLOGICAL IS PROBABLY THE

2590
02:16:41,360 --> 02:16:45,560
FIRST STEP THAT IS THE

2591
02:16:45,560 --> 02:16:46,120
APPROACH WE HAVE FOLLOWED SO

2592
02:16:46,120 --> 02:16:46,320
FAR.

2593
02:16:46,320 --> 02:16:46,800
IT DOES PRESUPPOSE THAT

2594
02:16:46,800 --> 02:16:48,600
EVENTUALLY BE EFFICACY IS

2595
02:16:48,600 --> 02:16:51,920
ABUNDANCE AND THIS MAY NOT BE

2596
02:16:51,920 --> 02:16:53,120
THE RIGHT ASSUMPTION BUT IT

2597
02:16:53,120 --> 02:16:55,880
SEEMS TO BE WORKING SO FAR

2598
02:16:55,880 --> 02:16:57,120
GIVEN WHAT EVERYONE HAS

2599
02:16:57,120 --> 02:17:00,920
COMMENTED ON THE COMPLEXITY

2600
02:17:00,920 --> 02:17:02,000
THAT COULD WELL BE THAT YOU

2601
02:17:02,000 --> 02:17:03,800
DON'T NEED A BUNCH OF BACTERIA

2602
02:17:03,800 --> 02:17:07,880
TO BE PRESENT.

2603
02:17:07,880 --> 02:17:09,320
THINK IS UNDER 20 PERCENT OF

2604
02:17:09,320 --> 02:17:13,920
THE MICROBIOTA.

2605
02:17:13,920 --> 02:17:16,600
AND THAT'S WHERE WE START SO

2606
02:17:16,600 --> 02:17:23,680
WHAT EXPOSURE CONSTITUTES.

2607
02:17:23,680 --> 02:17:31,080
AND WITH THAT MICROBIOTA.

2608
02:17:31,080 --> 02:17:32,880
AND THEN TO DO THAT

2609
02:17:32,880 --> 02:17:35,600
MATHEMATICAL BOOST THAT CAN

2610
02:17:35,600 --> 02:17:39,720
HELP YOU UNDERSTAND TO

2611
02:17:39,720 --> 02:17:43,720
INTRODUCING THE DRUG.

2612
02:17:43,720 --> 02:17:47,720
IN THIS HAS TO BE SUPPLEMENTED

2613
02:17:47,720 --> 02:17:49,040
AND AS WE CONTINUE IN THE

2614
02:17:49,040 --> 02:17:52,520
FUTURE OF CLINICAL TRIALS WITH

2615
02:17:52,520 --> 02:17:53,520
OTHER MEASURES THAT ARE NOT

2616
02:17:53,520 --> 02:17:54,120
SOLELY ABUNDANT SPACE BUT OF

2617
02:17:54,120 --> 02:18:03,760
COURSE CERTAIN CONCEPTS AND

2618
02:18:03,760 --> 02:18:05,520
THEN TO THINK ABOUT IT

2619
02:18:05,520 --> 02:18:11,520
FUNDAMENTALLY DIFFERENTLY.

2620
02:18:11,520 --> 02:18:12,000
>> SO ONE THING I WAS

2621
02:18:12,000 --> 02:18:13,560
WONDERING IS THAT MOST OF YOUR

2622
02:18:13,560 --> 02:18:16,800
ASSESSMENTS AND PRESENCE OF

2623
02:18:16,800 --> 02:18:18,080
MACRO ORGANISMS WE LOVE THAT

2624
02:18:18,080 --> 02:18:19,120
YOU ARE DOING SPECIFIC

2625
02:18:19,120 --> 02:18:20,920
SEQUENCE SO YOU CAN ASSESS IF

2626
02:18:20,920 --> 02:18:28,720
WHAT YOU PUT IN.

2627
02:18:28,720 --> 02:18:30,120
SO WE LOOKING AT WHAT'S COMING

2628
02:18:30,120 --> 02:18:30,720
OUT IN THE FECES OR WHAT IS IN

2629
02:18:30,720 --> 02:18:33,120
C TO?

2630
02:18:33,120 --> 02:18:37,480
AND FROM YOUR DOSE-RESPONSE A

2631
02:18:37,480 --> 02:18:37,960
FACT YOU CAN SEE A GOOD

2632
02:18:37,960 --> 02:18:38,560
RESPONSE AT LOW DOSES AS WELL

2633
02:18:38,560 --> 02:18:43,960
TO SUGGEST IT HAS TO BE LIVE

2634
02:18:43,960 --> 02:18:45,280
AND A WAY TO REPLICATE SO THAT

2635
02:18:45,280 --> 02:18:46,520
ANSWERS ONE OF THE OLD

2636
02:18:46,520 --> 02:18:55,840
QUESTIONS FROM THE FIELD

2637
02:18:55,840 --> 02:18:56,040
FIELD.

2638
02:18:56,040 --> 02:18:56,600
>> WHAT IF THAT IS ASSAY IN

2639
02:18:56,600 --> 02:18:58,040
WHAT'S GOING ON THE INSIDE?

2640
02:18:58,040 --> 02:19:02,760
YOU MAY THINK MORE AWAY, SO

2641
02:19:02,760 --> 02:19:08,960
WHAT YOU THINK QUICK.

2642
02:19:08,960 --> 02:19:09,520
>> THAT'S A GREAT QUESTION.

2643
02:19:09,520 --> 02:19:17,320
EVERYTHING THAT I SHOWED AND

2644
02:19:17,320 --> 02:19:17,920
WITH THE PRESENTATION TO BE

2645
02:19:17,920 --> 02:19:23,160
VERY INTERESTING LIKE SPEED

2646
02:19:23,160 --> 02:19:30,000
AND HABITAT AND THAT ABILITY

2647
02:19:30,000 --> 02:19:33,840
TO LATCH ONTO CERTAIN

2648
02:19:33,840 --> 02:19:36,560
HABITATS, THAT IS AN ASPECT

2649
02:19:36,560 --> 02:19:41,920
THAT WE HAVE NOT COVERED INTO

2650
02:19:41,920 --> 02:19:43,000
QUANTIFY THE AMOUNT OF THE BUG

2651
02:19:43,000 --> 02:19:46,240
AND TO YOUR OTHER QUESTION I

2652
02:19:46,240 --> 02:19:48,080
THINK WE NEED TO FIND A WAY TO

2653
02:19:48,080 --> 02:19:55,720
DISTINGUISH WASHOUT OF DRUG IN

2654
02:19:55,720 --> 02:19:56,920
AND DRUG OUT OF WHAT TO EXPECT

2655
02:19:56,920 --> 02:19:58,840
AND WHAT TYPE OF DYNAMICS IF

2656
02:19:58,840 --> 02:20:03,080
YOU SEE ACTIVE REPLICATION?

2657
02:20:03,080 --> 02:20:05,600
AND THEN WHAT YOU START TO

2658
02:20:05,600 --> 02:20:08,920
IMPLEMENT SO THAT IS MORE IN

2659
02:20:08,920 --> 02:20:10,400
LINE OF ACTIVE REPLICATION

2660
02:20:10,400 --> 02:20:18,920
FROM WHAT YOU WERE SUGGESTING.

2661
02:20:18,920 --> 02:20:23,520
>> AND THEN TO DISTINGUISH

2662
02:20:23,520 --> 02:20:24,080
WASHINGTON AND WASHOUT FROM

2663
02:20:24,080 --> 02:20:26,120
COLONIZATION PER SE.

2664
02:20:26,120 --> 02:20:29,240
>> YES.

2665
02:20:29,240 --> 02:20:36,480
>> .

2666
02:20:36,480 --> 02:20:39,000
>> AND SO WITH YOUR HUMAN

2667
02:20:39,000 --> 02:20:41,840
TRIALS AND JUST THINKING BACK

2668
02:20:41,840 --> 02:20:49,520
TO THE SMALL MOLECULE BASE DID

2669
02:20:49,520 --> 02:20:50,040
YOU DO ANYTHING THAT WAS

2670
02:20:50,040 --> 02:20:50,840
DIETARY OR STANDARDIZATION?

2671
02:20:50,840 --> 02:20:56,320
>> WITH THE PHASE ONE STUDIES

2672
02:20:56,320 --> 02:21:00,000
WE DO HAVE CONTROL DURING THE

2673
02:21:00,000 --> 02:21:05,320
DOSING BUT BEYOND THAT WHILE

2674
02:21:05,320 --> 02:21:06,160
YOU CAN PROVIDE GUIDELINES IT

2675
02:21:06,160 --> 02:21:08,360
IS ONE OF THE CHALLENGES WITH

2676
02:21:08,360 --> 02:21:11,920
THIS ENDEAVOR PEOPLE EAT WHAT

2677
02:21:11,920 --> 02:21:14,320
THEY WANT.

2678
02:21:14,320 --> 02:21:15,200
SO WE CAN MAKE RECOMMENDATIONS

2679
02:21:15,200 --> 02:21:18,640
AND COLLECT DATA, BUT THESE

2680
02:21:18,640 --> 02:21:19,760
HAVE ALL BEEN REALLY HARD FOR

2681
02:21:19,760 --> 02:21:20,480
US TO DO.

2682
02:21:20,480 --> 02:21:27,360
IN AN IDEAL WORLD WE COULD

2683
02:21:27,360 --> 02:21:34,640
AGAIN PRIME THE MICROBIOTA FOR

2684
02:21:34,640 --> 02:21:35,200
WITH PREBIOTIC CERTAIN DIET

2685
02:21:35,200 --> 02:21:35,560
RECOMMENDATIONS.

2686
02:21:35,560 --> 02:21:36,200
BUT IT HAS BEEN CHALLENGING TO

2687
02:21:36,200 --> 02:21:40,920
DO THAT GIVEN COMPLIANCE

2688
02:21:40,920 --> 02:21:41,800
ISSUES AND THE ABILITY TO

2689
02:21:41,800 --> 02:21:44,040
COLLECT DATA AT THAT LEVEL SO

2690
02:21:44,040 --> 02:21:46,520
SOME OF THE VERY PRACTICAL

2691
02:21:46,520 --> 02:21:52,280
THINGS WITH THIS KIND OF WORK

2692
02:21:52,280 --> 02:21:53,440
THAT WAS MENTIONED HAS GOTTEN

2693
02:21:53,440 --> 02:21:55,200
IN THE WAY TO ALLOW US TO

2694
02:21:55,200 --> 02:22:03,520
CONTROL FOR DIET.

2695
02:22:03,520 --> 02:22:05,320
>> AND A QUICK ONE TO MARK TO

2696
02:22:05,320 --> 02:22:07,480
COMPLETELY UNDERSTAND OF

2697
02:22:07,480 --> 02:22:12,600
PATIENT COMPLIANCE.

2698
02:22:12,600 --> 02:22:13,920
WHAT ABOUT PROPER DELIVERY TO

2699
02:22:13,920 --> 02:22:19,880
THE CORRECT BIO?

2700
02:22:19,880 --> 02:22:21,920
BIO?

2701
02:22:21,920 --> 02:22:22,480
AND THEN TO OPTIMIZE THAT?

2702
02:22:22,480 --> 02:22:25,520
>> IT'S A GREAT QUESTION AND

2703
02:22:25,520 --> 02:22:30,480
THE OPPORTUNITIES WITH THOSE

2704
02:22:30,480 --> 02:22:37,520
MECHANISMS AND GO BACK TO THE

2705
02:22:37,520 --> 02:22:41,000
STABILITY OF THE ORGANISMS

2706
02:22:41,000 --> 02:22:43,560
THOSE FROM WHICH THEY ARE

2707
02:22:43,560 --> 02:22:50,840
SEPARATED SO IT IS OF INTEREST

2708
02:22:50,840 --> 02:22:51,440
YOU DON'T JUST WANT TO TAKE IT

2709
02:22:51,440 --> 02:22:53,400
IN AND MEASURE WHAT'S COMING

2710
02:22:53,400 --> 02:22:58,080
OUT THOSE OPPORTUNITIES TO

2711
02:22:58,080 --> 02:23:04,000
PRIME THE ECOSYSTEM SO THERE

2712
02:23:04,000 --> 02:23:07,760
ARE DIFFERENT APPROACHES AND

2713
02:23:07,760 --> 02:23:12,680
TO BE EVALUATED AS WELL AS THE

2714
02:23:12,680 --> 02:23:18,520
MECHANISMS TO STUDY THAT AND

2715
02:23:18,520 --> 02:23:20,120
ALL THE TOOLS THAT ARE

2716
02:23:20,120 --> 02:23:29,800
INVESTIGATED WITH THAT

2717
02:23:29,800 --> 02:23:36,360
ENDOSCOPY IT'S A CHALLENGE BUT

2718
02:23:36,360 --> 02:23:36,960
A QUESTIONS OF HOW DO YOU GET

2719
02:23:36,960 --> 02:23:38,880
THAT PERSISTENCE QUICK.

2720
02:23:38,880 --> 02:23:40,600
>> .

2721
02:23:40,600 --> 02:23:44,840
SO, COMING BACK TO THE

2722
02:23:44,840 --> 02:23:50,840
DISCUSSION OF BIOAVAILABILITY

2723
02:23:50,840 --> 02:23:51,840
AS WE DANCE FROM ASSOCIATIONS

2724
02:23:51,840 --> 02:23:55,120
OF ORGANISMS TO CLINICAL

2725
02:23:55,120 --> 02:23:59,520
OUTCOME AND ACTION WE KNOW THE

2726
02:23:59,520 --> 02:24:03,720
MOLECULES THAT ARE SECRETED

2727
02:24:03,720 --> 02:24:06,240
AND WE CAN DO MORE TRADITIONAL

2728
02:24:06,240 --> 02:24:10,000
STUDIES WHERE THE MOLECULES

2729
02:24:10,000 --> 02:24:13,920
ENTER THE CIRCULATION.

2730
02:24:13,920 --> 02:24:21,480
THIS IS A RETRACTABLE PROBLEM

2731
02:24:21,480 --> 02:24:22,040
FOR THOSE THAT ARE CURRENTLY

2732
02:24:22,040 --> 02:24:22,600
STUDIED TO DEFINE THEMSELVES

2733
02:24:22,600 --> 02:24:27,520
AT THE MOLECULAR LEVEL SO I

2734
02:24:27,520 --> 02:24:29,120
PUSHED GOING BEYOND JUST

2735
02:24:29,120 --> 02:24:29,680
ORGANISMS TO UNDERSTAND WHAT

2736
02:24:29,680 --> 02:24:38,480
ARE THE CHEMICAL INTERACTIONS.

2737
02:24:38,480 --> 02:24:43,600
>> I HAVE A QUESTION FOR YOU

2738
02:24:43,600 --> 02:24:49,960
JUST FROM THE PERSPECTIVE OF

2739
02:24:49,960 --> 02:24:51,320
YOUR VANTAGE POINT WHAT IS THE

2740
02:24:51,320 --> 02:24:58,720
ROLE OF COMBINING CAPACITY AS

2741
02:24:58,720 --> 02:25:00,000
AN ADVANTAGE STRATEGICALLY TO

2742
02:25:00,000 --> 02:25:03,760
UNDERSTAND BETTER THROUGH YOUR

2743
02:25:03,760 --> 02:25:05,560
OREGON AS ONE -- ORGANISMS AND

2744
02:25:05,560 --> 02:25:10,280
ALSO TO UNDERSTAND METABOLIC

2745
02:25:10,280 --> 02:25:13,200
FUNCTIONS EXPRESSES THOSE

2746
02:25:13,200 --> 02:25:17,800
MICROBIAL COMMUNITIES?

2747
02:25:17,800 --> 02:25:25,040
>> SO I THINK THAT WE HAVE NOT

2748
02:25:25,040 --> 02:25:26,920
LEVERAGED AS MUCH AS I WOULD

2749
02:25:26,920 --> 02:25:31,400
LIKE IN THAT DIRECTION BUT ONE

2750
02:25:31,400 --> 02:25:33,320
THING WE'RE DOING RIGHT NOW

2751
02:25:33,320 --> 02:25:38,120
EVEN WITH MEADOW GENOMICS DATA

2752
02:25:38,120 --> 02:25:41,760
FROM WHAT IS IN OUR DATABASES

2753
02:25:41,760 --> 02:25:45,800
AND THEN THOSE THAT ARE IN THE

2754
02:25:45,800 --> 02:25:46,400
SESSION BUT THAT ALLOWS US TO

2755
02:25:46,400 --> 02:25:49,120
GET BEYOND THAT.

2756
02:25:49,120 --> 02:25:53,080
IF WE ARE ABLE TO INVESTIGATE

2757
02:25:53,080 --> 02:25:53,840
SIGNATURES ON FOR SPONSORING A

2758
02:25:53,840 --> 02:25:56,120
TALKED ABOUT TODAY IS EQUAL

2759
02:25:56,120 --> 02:25:59,520
BUT WE HAVE STUDIES AS WELL

2760
02:25:59,520 --> 02:26:08,520
AND THE QUESTION IS AND WITH

2761
02:26:08,520 --> 02:26:12,400
THAT POSITIVE OUTCOMES AND CAN

2762
02:26:12,400 --> 02:26:16,480
WE MAP THOSE BACK TO A

2763
02:26:16,480 --> 02:26:17,520
PARTICULAR FUNCTIONS OF THIS

2764
02:26:17,520 --> 02:26:19,320
IS THE ANALYSIS WE ARE

2765
02:26:19,320 --> 02:26:23,120
STARTING TO DO.

2766
02:26:23,120 --> 02:26:27,640
AND THE WORK THAT YOU SHARED

2767
02:26:27,640 --> 02:26:31,000
IS WHAT I LIKE TO DO IN THE

2768
02:26:31,000 --> 02:26:32,680
CLINICAL COHORTS TO

2769
02:26:32,680 --> 02:26:35,720
INVESTIGATE THE WAYS THROUGH

2770
02:26:35,720 --> 02:26:40,960
THE RESIDENT COMMUNITY AND

2771
02:26:40,960 --> 02:26:44,440
WHAT CAN BE ATTRIBUTED.

2772
02:26:44,440 --> 02:26:48,720
>> I GUESS THAT IS AN

2773
02:26:48,720 --> 02:26:52,120
OPPORTUNITY TO LOOK AT

2774
02:26:52,120 --> 02:26:56,640
EXPRESSION AND SMALL ARE AND A

2775
02:26:56,640 --> 02:27:02,680
METHODS ARE IMPROVED WITH

2776
02:27:02,680 --> 02:27:03,320
SEQUENCING TO DETERMINE WHAT

2777
02:27:03,320 --> 02:27:05,120
SIGNALING AND METABOLIC

2778
02:27:05,120 --> 02:27:07,080
PATHWAYS IN THAT COMMUNITY

2779
02:27:07,080 --> 02:27:08,120
CONTEXT SO I DO THINK IT

2780
02:27:08,120 --> 02:27:14,400
TECHNICAL ISSUE IS TO GET THAT

2781
02:27:14,400 --> 02:27:18,800
DEPLETION ACHIEVED EFFICIENTLY

2782
02:27:18,800 --> 02:27:20,720
SO YOU DON'T HAVE TO WASTE SO

2783
02:27:20,720 --> 02:27:24,920
MUCH OF YOUR INVESTMENT ON

2784
02:27:24,920 --> 02:27:26,080
THOSE SEQUENCES.

2785
02:27:26,080 --> 02:27:31,960
THANK YOU.

2786
02:27:31,960 --> 02:27:39,320
>> I WILL READ THIS QUESTION

2787
02:27:39,320 --> 02:27:39,800
AND IS THAT ON ANY OTHER

2788
02:27:39,800 --> 02:27:43,560
SPEAKERS THAT WANT TO COMMENT

2789
02:27:43,560 --> 02:27:51,840
IN DESIGNING SYNTHETIC PLASTIC

2790
02:27:51,840 --> 02:27:53,800
TECHNOLOGIES?

2791
02:27:53,800 --> 02:27:58,720
>> SYNTHETIC PLASMID

2792
02:27:58,720 --> 02:27:59,920
TECHNOLOGY?

2793
02:27:59,920 --> 02:28:02,920
>> THAT IS THE TECHNOLOGY ON

2794
02:28:02,920 --> 02:28:05,120
-- QUESTION, YES.

2795
02:28:05,120 --> 02:28:08,960
>> I DON'T KNOW IF I CAN MAKE

2796
02:28:08,960 --> 02:28:13,720
ANY EXPLICIT COMMENTS.

2797
02:28:13,720 --> 02:28:14,720
BUT FROM THE PERSPECTIVE OF

2798
02:28:14,720 --> 02:28:20,920
THE PUBLIC MOVING FORWARD WITH

2799
02:28:20,920 --> 02:28:26,520
THE FIRST CONSORTIA INCLUDING

2800
02:28:26,520 --> 02:28:26,960
GENETICALLY ENGINEERED

2801
02:28:26,960 --> 02:28:27,240
ORGANISMS.

2802
02:28:27,240 --> 02:28:28,680
I THINK IT WILL BE VERY

2803
02:28:28,680 --> 02:28:31,160
IMPORTANT TO HAVE THE PUBLIC

2804
02:28:31,160 --> 02:28:34,000
UNDERSTAND THAT NATURALLY

2805
02:28:34,000 --> 02:28:35,840
OCCURRING ORGANISMS CAN BE

2806
02:28:35,840 --> 02:28:38,360
ASSEMBLED TO SPECIFIC

2807
02:28:38,360 --> 02:28:44,480
FUNCTIONS TO PROVIDE FUNCTIONS

2808
02:28:44,480 --> 02:28:45,480
THAT ARE NOT EXPRESSED BY A

2809
02:28:45,480 --> 02:28:50,000
MICROBIAL COMMUNITY AND

2810
02:28:50,000 --> 02:28:51,120
ALTHOUGH FROM A RESEARCH

2811
02:28:51,120 --> 02:28:52,520
PERSPECTIVE THE SYNTHETIC

2812
02:28:52,520 --> 02:28:58,800
BIOLOGY AND WITH THAT IMPACT

2813
02:28:58,800 --> 02:29:01,760
ON PUBLIC ACCEPTANCE SO THE

2814
02:29:01,760 --> 02:29:05,800
FIELD HAS TO BE VERY MINDFUL

2815
02:29:05,800 --> 02:29:06,040
MINDFUL.

2816
02:29:06,040 --> 02:29:07,880
AND ALSO THE IDEA OF A KILL

2817
02:29:07,880 --> 02:29:10,720
SWITCH HOW DO YOU DOSE

2818
02:29:10,720 --> 02:29:12,880
SOMETHING THAT IS GENETICALLY

2819
02:29:12,880 --> 02:29:17,240
ENGINEERED?

2820
02:29:17,240 --> 02:29:22,600
AND NATURE HANDS TAUGHT US

2821
02:29:22,600 --> 02:29:26,920
THAT IS A FANTASY THAT IS MY

2822
02:29:26,920 --> 02:29:31,600
TWO CENTS.

2823
02:29:31,600 --> 02:29:34,280
>> IT'S VERY DIFFICULT SINCE

2824
02:29:34,280 --> 02:29:41,760
WE DON'T KNOW YET.

2825
02:29:41,760 --> 02:29:42,120
HOW THAT WORKS.

2826
02:29:42,120 --> 02:29:45,600
DOES ANYBODY ELSE WANT TO

2827
02:29:45,600 --> 02:29:51,160
COMMENT?

2828
02:29:51,160 --> 02:29:53,920
IF NOT THEN I'LL GO TO A

2829
02:29:53,920 --> 02:29:57,680
DIFFERENT TYPE OF QUESTION.

2830
02:29:57,680 --> 02:29:58,280
THOSE THAT ARE PREDICTING THE

2831
02:29:58,280 --> 02:30:00,240
OUTCOMES HAVE TO BE FULLY

2832
02:30:00,240 --> 02:30:02,440
DEFINED FOR THAT GUIDANCE THAT

2833
02:30:02,440 --> 02:30:14,760
IS TOO CONSTRICTING?

2834
02:30:14,760 --> 02:30:15,160
>> IT'S DEFINITELY

2835
02:30:15,160 --> 02:30:15,800
CONSTRICTING THERE ARE REASONS

2836
02:30:15,800 --> 02:30:22,400
FOR THAT BUYS SECONDARY OR THE

2837
02:30:22,400 --> 02:30:25,280
TERTIARY OUTCOMES SO I THINK

2838
02:30:25,280 --> 02:30:31,560
THERE IS A RATIONALE FOR THAT

2839
02:30:31,560 --> 02:30:33,240
BUT THEY ARE CONSTRICTING AND

2840
02:30:33,240 --> 02:30:33,840
HAVE AN ANSWER IF THEY ARE TOO

2841
02:30:33,840 --> 02:30:38,800
CONSTRICTING BUT IT DEFINITELY

2842
02:30:38,800 --> 02:30:39,320
HAS TO BE THOUGHT ABOUT AS

2843
02:30:39,320 --> 02:30:43,600
FIRST-LINE OF MEDICINE BUT

2844
02:30:43,600 --> 02:30:44,920
THERE ARE SOME GOOD EXAMPLES

2845
02:30:44,920 --> 02:30:49,600
FOR PERSONALIZED MEDICINE.

2846
02:30:49,600 --> 02:30:51,720
>> ANYONE TO STOP ANYTHING

2847
02:30:51,720 --> 02:30:57,320
THAT STANDARD CLINICAL TRIAL

2848
02:30:57,320 --> 02:30:57,880
WITHOUT PRIMARY OR SECONDARY

2849
02:30:57,880 --> 02:30:58,440
OUTCOMES AND THEN WHAT THEY

2850
02:30:58,440 --> 02:30:58,720
LOOKED AT?

2851
02:30:58,720 --> 02:31:02,040
IS THERE ANYTHING TO STOP THEM

2852
02:31:02,040 --> 02:31:03,200
THAT THIS IS SOMETHING WE

2853
02:31:03,200 --> 02:31:04,680
COULD FOLLOW UP IN THE NEXT

2854
02:31:04,680 --> 02:31:07,680
TRIAL?

2855
02:31:07,680 --> 02:31:08,960
>> THEY CAN DO THAT FOR SURE

2856
02:31:08,960 --> 02:31:09,920
BUT THEY CANNOT REPORTED AS

2857
02:31:09,920 --> 02:31:10,920
PRIMARY AND THAT'S IT THEY'VE

2858
02:31:10,920 --> 02:31:20,520
DONE IN THE PAST SO THEY CAN

2859
02:31:20,520 --> 02:31:21,120
DEFINITELY REPORTED THEY JUST

2860
02:31:21,120 --> 02:31:21,680
NEED TO BE HONEST ABOUT IT

2861
02:31:21,680 --> 02:31:22,120
IT'S IMPORTANT FOR NEW

2862
02:31:22,120 --> 02:31:23,320
APPLICATIONS AND RESEARCH IT

2863
02:31:23,320 --> 02:31:27,000
JUST NEEDS TO BE HONEST.

2864
02:31:27,000 --> 02:31:32,800
>> SO AFTER THE STUDIES WE

2865
02:31:32,800 --> 02:31:35,520
WANT PEOPLE TO COME BACK AND

2866
02:31:35,520 --> 02:31:36,720
USING THE DATA THERE IS SO

2867
02:31:36,720 --> 02:31:38,920
MUCH MORE TO LEARN AND WITH

2868
02:31:38,920 --> 02:31:42,360
THAT INVESTMENT COMING UP WITH

2869
02:31:42,360 --> 02:31:49,760
NIH AND THEN WE ADVOCATE AN

2870
02:31:49,760 --> 02:31:51,000
OPEN SCIENCE IS THE AREA WE

2871
02:31:51,000 --> 02:31:55,200
ARE LIVING IN AND THEN

2872
02:31:55,200 --> 02:31:57,800
RESEARCH IS MADE PUBLIC AND

2873
02:31:57,800 --> 02:32:02,920
THE WHOLE COMMUNITY AND THEN

2874
02:32:02,920 --> 02:32:09,960
TO REDISCOVER AND THE COMMENT

2875
02:32:09,960 --> 02:32:12,520
RESOURCES AND TO MAKE AN

2876
02:32:12,520 --> 02:32:14,800
IMPACT.

2877
02:32:14,800 --> 02:32:21,920
>> WE HAVE THREE HANDSET.

2878
02:32:21,920 --> 02:32:28,720
ONE -- HANDS UP.

2879
02:32:28,720 --> 02:32:31,720
>> I HAVE A QUESTION FOR YOU

2880
02:32:31,720 --> 02:32:33,720
BECAUSE IN DEALING WITH

2881
02:32:33,720 --> 02:32:36,120
MICROBIOTA BASED CLINICAL

2882
02:32:36,120 --> 02:32:40,000
TRIAL TRIALS, IT'S VERY TOUGH

2883
02:32:40,000 --> 02:32:40,520
TO GET A SINGLE PRIMARY

2884
02:32:40,520 --> 02:32:43,480
OUTCOME MEASURE WHEN YOU ARE

2885
02:32:43,480 --> 02:32:43,880
TRYING TO NOT ONLY

2886
02:32:43,880 --> 02:32:44,560
RECONFIGURATION OF THE

2887
02:32:44,560 --> 02:32:47,240
MICROBIOTA ITSELF SO YOU RUN

2888
02:32:47,240 --> 02:32:49,680
INTO A PROBLEM WITH

2889
02:32:49,680 --> 02:32:50,600
TRADITIONAL HIGH-IMPACT

2890
02:32:50,600 --> 02:32:55,000
CLINICAL JOURNALS DEALING WITH

2891
02:32:55,000 --> 02:32:58,840
THAT AND THEN OF COURSE THE

2892
02:32:58,840 --> 02:33:10,480
ISSUE OF FDR AND ACHIEVE

2893
02:33:10,480 --> 02:33:11,000
STATISTICAL SIGNIFICANCE.

2894
02:33:11,000 --> 02:33:11,600
I'M NOT SAYING THIS IS A VERY

2895
02:33:11,600 --> 02:33:15,440
CLEAR WAY BUT MICROBIOTA BASED

2896
02:33:15,440 --> 02:33:16,760
INTERVENTIONS TRYING TO

2897
02:33:16,760 --> 02:33:21,960
CONNECT THAT COMMUNITY CREATES

2898
02:33:21,960 --> 02:33:26,280
A DUALITY THAT MAKES THAT

2899
02:33:26,280 --> 02:33:27,000
INITIAL DESCRIPTION FOR

2900
02:33:27,000 --> 02:33:27,560
CLINICAL TRIALS SOMEWHAT

2901
02:33:27,560 --> 02:33:29,720
CHALLENGING.

2902
02:33:29,720 --> 02:33:33,720
I DON'T KNOW IF YOU HAVE ANY

2903
02:33:33,720 --> 02:33:34,720
VISUAL OR MICROBIAL OR

2904
02:33:34,720 --> 02:33:39,360
CEREBRAL RESPONSE?

2905
02:33:39,360 --> 02:33:39,800
>> I AGREE WITH YOU.

2906
02:33:39,800 --> 02:33:42,760
>> BUT AT THE SAME TIME IF YOU

2907
02:33:42,760 --> 02:33:47,600
JUST SAY WE WILL SEE CHANGES

2908
02:33:47,600 --> 02:33:51,800
THEN YOU PROBABLY WELL.

2909
02:33:51,800 --> 02:33:52,880
DID YOU THINK ABOUT THEM

2910
02:33:52,880 --> 02:33:53,120
BEFORE?

2911
02:33:53,120 --> 02:33:54,440
DOES THAT MAKE SENSE?

2912
02:33:54,440 --> 02:34:01,480
BUT I AGREE BUT A LOT OF THIS

2913
02:34:01,480 --> 02:34:02,920
IS BEGINNING AND THEN YOU HAVE

2914
02:34:02,920 --> 02:34:12,720
TO JUST PICK A TIME FRAME.

2915
02:34:12,720 --> 02:34:20,120
>> WE HAVE FIVE MORE MINUTES

2916
02:34:20,120 --> 02:34:21,040
SO IF ANYBODY ELSE HAS

2917
02:34:21,040 --> 02:34:24,840
SOMETHING THEY WANT TO SAY FOR

2918
02:34:24,840 --> 02:34:28,720
THE LAST TWO OR THREE MINUTES

2919
02:34:28,720 --> 02:34:28,920
QUICK.

2920
02:34:28,920 --> 02:34:30,320
>> I JUST WANT TO MAKE A BRIEF

2921
02:34:30,320 --> 02:34:34,000
COMMENT ON THE QUESTION OF THE

2922
02:34:34,000 --> 02:34:35,960
REQUIREMENT TO DECLARE PRIMARY

2923
02:34:35,960 --> 02:34:38,920
OUTCOMES OR SECONDARY

2924
02:34:38,920 --> 02:34:39,200
OUTCOMES?

2925
02:34:39,200 --> 02:34:43,520
>> IT IS RESTRICTED BUT

2926
02:34:43,520 --> 02:34:46,720
NECESSARY THAT WAS POINTED OUT

2927
02:34:46,720 --> 02:34:48,920
BECAUSE THE SHEER NUMBER OF

2928
02:34:48,920 --> 02:34:53,120
THINGS GIVEN THAT THIS FIELD

2929
02:34:53,120 --> 02:34:54,160
IS NEW WHEN IT COMES TO MANY

2930
02:34:54,160 --> 02:34:58,480
OF THESE TRANSLATIONS OR

2931
02:34:58,480 --> 02:35:00,360
APPLICATIONS CAN MEAN IF WE

2932
02:35:00,360 --> 02:35:02,400
ARE NOT CAREFUL WE COULD END

2933
02:35:02,400 --> 02:35:10,600
UP IN A SITUATION WHERE THIS

2934
02:35:10,600 --> 02:35:12,000
WE ARE CLEARLY DEFINING OUR

2935
02:35:12,000 --> 02:35:12,600
OUTCOMES AND THAT DOESN'T TAKE

2936
02:35:12,600 --> 02:35:15,080
AWAY FROM THE FACT THOSE

2937
02:35:15,080 --> 02:35:16,120
OUTCOMES THAT ARE

2938
02:35:16,120 --> 02:35:16,720
UNDERSTANDING ARE VERY LIMITED

2939
02:35:16,720 --> 02:35:18,520
SO THERE WILL BE THE

2940
02:35:18,520 --> 02:35:20,920
ADJUSTMENT PERIOD OR A PAIN

2941
02:35:20,920 --> 02:35:25,040
PERIOD WHY WE DEVELOPED AN

2942
02:35:25,040 --> 02:35:26,040
UNDERSTANDING TO GET TO THE

2943
02:35:26,040 --> 02:35:28,560
POINT AS MENTIONED THAT WHEN

2944
02:35:28,560 --> 02:35:31,040
WE KNOW IT IS A PARTICULAR

2945
02:35:31,040 --> 02:35:36,720
MOLECULE AND WHAT IS THE

2946
02:35:36,720 --> 02:35:36,960
MECHANISM?

2947
02:35:36,960 --> 02:35:37,520
ONCE YOU KNOW THE MECHANISM

2948
02:35:37,520 --> 02:35:41,200
YOU CAN DEFINE YOUR OUTCOME

2949
02:35:41,200 --> 02:35:42,120
PRIOR TO THE TRIAL WITH MUCH

2950
02:35:42,120 --> 02:35:46,880
MORE CONFIDENCE AND LESS FEAR

2951
02:35:46,880 --> 02:35:55,400
OF THE EFFICACY SO THEN TO

2952
02:35:55,400 --> 02:35:57,160
DEFINE THE OUTCOMES THERE

2953
02:35:57,160 --> 02:35:59,400
COULD BE A PERIOD WHAT TO LOOK

2954
02:35:59,400 --> 02:36:01,680
FOR AND NOT ENTIRELY

2955
02:36:01,680 --> 02:36:12,960
SUCCESSFUL.

2956
02:36:12,960 --> 02:36:13,560
>> WE ARE GOING TO ADD TO THAT

2957
02:36:13,560 --> 02:36:14,520
WITH THE REGULATORY

2958
02:36:14,520 --> 02:36:18,320
REQUIREMENTS BECAUSE IT'S IN

2959
02:36:18,320 --> 02:36:23,880
ITS INFANCY AND WITH THOSE

2960
02:36:23,880 --> 02:36:25,120
PROACTIVE CONVERSATIONS WITH

2961
02:36:25,120 --> 02:36:29,480
THOSE REGULATORY AND AGENCIES

2962
02:36:29,480 --> 02:36:30,080
THOSE KINDS OF THINGS CAN BE

2963
02:36:30,080 --> 02:36:36,920
HELPFUL AGAIN.

2964
02:36:36,920 --> 02:36:38,480
IS THAT ARE BIO TERRY

2965
02:36:38,480 --> 02:36:41,480
SUPPLEMENT HAVING THOSE

2966
02:36:41,480 --> 02:36:46,720
PROACTIVE CONVERSATIONS AND

2967
02:36:46,720 --> 02:36:48,200
THAT IS NOT NECESSARILY

2968
02:36:48,200 --> 02:36:52,560
MEANINGFUL BUT THAT DOES NEED

2969
02:36:52,560 --> 02:36:55,720
TO BE DEFINED IT DOESN'T MAKE

2970
02:36:55,720 --> 02:37:00,320
IT EASY FOR THOSE OF THE

2971
02:37:00,320 --> 02:37:08,440
REASONS.

2972
02:37:08,440 --> 02:37:09,480
>> WE HAVE TWO MORE MINUTES IF

2973
02:37:09,480 --> 02:37:11,120
ANYBODY WANTS TO SAY SOMETHING

2974
02:37:11,120 --> 02:37:27,760
BEFORE THEY BREAK FOR LUNCH?

2975
02:37:27,760 --> 02:37:28,280
AND NOW I SAID THE WORD

2976
02:37:28,280 --> 02:37:28,480
LUNCH.

2977
02:37:28,480 --> 02:37:28,720
[LAUGHTER]

2978
02:37:28,720 --> 02:37:32,760
THANK YOU SO MUCH THANK YOU

2979
02:37:32,760 --> 02:37:36,920
FOR CO- MODERATING THIS

2980
02:37:36,920 --> 02:37:39,920
SESSION WITH ME.

2981
02:37:39,920 --> 02:37:41,320
I HOPE YOU WILL KEEP IN TOUCH

2982
02:37:41,320 --> 02:37:44,120
WITH US LET US KNOW THE

2983
02:37:44,120 --> 02:37:46,440
PROGRESS AND LET US HELP YOU

2984
02:37:46,440 --> 02:37:49,880
AND TRY TO DO TOGETHER BETTER

2985
02:37:49,880 --> 02:37:57,880
RESEARCH AND MORE SPECIALIZED.

2986
02:37:57,880 --> 02:38:03,120
THANK YOU SO MUCH.

2987
02:38:03,120 --> 02:38:04,680
>> AND THANK YOU.

2988
02:38:04,680 --> 02:38:06,480
THAT WAS A GREAT DISCUSSION.

2989
02:38:06,480 --> 02:38:08,320
THAT DOES TAKE US INTO THE

2990
02:38:08,320 --> 02:38:10,040
LUNCH BREAK.

2991
02:38:10,040 --> 02:38:11,680
>> I WANT TO WELCOME 

2992
02:38:11,680 --> 02:38:13,040
EVERYBODY BACK FROM LUNCH. 

2993
02:38:13,040 --> 02:38:15,720
SO FOR OUR SECOND SESSION THIS 

2994
02:38:15,720 --> 02:38:19,640
IS GOING TO BE LED OUR SESSION 2

2995
02:38:19,640 --> 02:38:33,520
IS HOST MICROBIOME DR. VARGAS IS

2996
02:38:33,520 --> 02:38:37,160
FROM THE NATIONAL INSTITUTE OF 

2997
02:38:37,160 --> 02:38:39,520
CHILD HEALTH AND HUMAN 

2998
02:38:39,520 --> 02:38:41,440
DEVELOPMENT AND DR. HAMILTON IS 

2999
02:38:41,440 --> 02:38:43,240
FROM NIDDK. 

3000
02:38:43,240 --> 02:38:44,840
QUICK SLIDE SHOWS ALL THE 

3001
02:38:44,840 --> 02:38:46,200
SPEAKERS AND DR. HAMILTON IS 

3002
02:38:46,200 --> 02:38:48,320
GOING TO BE INTRODUCING OUR 

3003
02:38:48,320 --> 02:38:52,120
SESSION SPEAKERS AS EACH PERE 

3004
02:38:52,120 --> 02:38:53,520
PREPARES TO SHARE THEIR SLIDES. 

3005
02:38:53,520 --> 02:38:58,520
I'M GOING TO TURN IT OVER TO 

3006
02:38:58,520 --> 02:39:00,440
DR. HAMILTON. 

3007
02:39:00,440 --> 02:39:02,320
>> THANK YOU VERY MUCH KATHERINE

3008
02:39:02,320 --> 02:39:04,520
I WOULD LIKE TO THANK ALL THE 

3009
02:39:04,520 --> 02:39:06,760
ORGANIZERS FOR THE HARD WORK 

3010
02:39:06,760 --> 02:39:08,400
MAKING THE SUCH AN EXCITING 

3011
02:39:08,400 --> 02:39:11,200
MEETING AND THANK THE PREVIOUS 

3012
02:39:11,200 --> 02:39:12,200
SPEAKERS FOR THEIR OUTSTANDING 

3013
02:39:12,200 --> 02:39:12,600
TALKS. 

3014
02:39:12,600 --> 02:39:14,960
I WOULD LIKE TO REMIND THE 

3015
02:39:14,960 --> 02:39:15,840
PARTICIPANTS THAT THE PROGRAM 

3016
02:39:15,840 --> 02:39:17,520
BOOK IS AVAILABLE ONLINE AND 

3017
02:39:17,520 --> 02:39:20,600
ALSO WITH THE SPEAKERS ABSTRACTS

3018
02:39:20,600 --> 02:39:22,600
AND BIO SO PLEASE TAKE ADVANTAGE

3019
02:39:22,600 --> 02:39:23,280
OF THAT. 

3020
02:39:23,280 --> 02:39:27,320
I'M PLEASED TO COMODERATE THE 

3021
02:39:27,320 --> 02:39:31,960
SESSION WITH MY COLLEAGUE 

3022
02:39:31,960 --> 02:39:37,960
DR. ANGELA VARGAS. 

3023
02:39:37,960 --> 02:39:39,800
WE START WITH DR. SONNENBURG 

3024
02:39:39,800 --> 02:39:43,520
WITH THE ABUNDANCE OF NEXT 

3025
02:39:43,520 --> 02:39:45,640
GENERATION PROBIOTIC THERAPIES. 

3026
02:39:45,640 --> 02:39:47,760
DR. SONNENBURG THANK YOU VERY 

3027
02:39:47,760 --> 02:39:49,600
MUCH FOR JOINING US. 

3028
02:39:49,600 --> 02:39:50,440
>> RIGHT. 

3029
02:39:50,440 --> 02:39:51,680
THANKS VERY MUCH FOR THAT 

3030
02:39:51,680 --> 02:39:52,040
INTRODUCTION. 

3031
02:39:52,040 --> 02:39:53,760
IT'S A PLEASURE TO BE HERE. 

3032
02:39:53,760 --> 02:39:57,960
I WANT TO THANK THE ORGANIZERS 

3033
02:39:57,960 --> 02:39:59,760
AS WELL, THE COLLECTED KNOWLEDGE

3034
02:39:59,760 --> 02:40:02,960
IN THIS MEETING IS SUPER 

3035
02:40:02,960 --> 02:40:03,520
IMPRESSIVE. 

3036
02:40:03,520 --> 02:40:05,960
I'M SORRY WE COULDN'T ALL BE 

3037
02:40:05,960 --> 02:40:07,880
TOGETHER TO EAT AND CHAT AN 

3038
02:40:07,880 --> 02:40:09,320
EXCHANGE MORE IDEAS BUT 

3039
02:40:09,320 --> 02:40:10,520
WONDERFUL TO BE WITH YOU 

3040
02:40:10,520 --> 02:40:10,840
VIRTUALLY. 

3041
02:40:10,840 --> 02:40:14,360
SO THIS MORNING WE HEARD A LOT 

3042
02:40:14,360 --> 02:40:24,080
ABOUT PROBIOTIC OR MICROBAL 

3043
02:40:24,080 --> 02:40:26,960
THERAPIES AND THE INDIVIDUALITY 

3044
02:40:26,960 --> 02:40:29,800
OF THE MICROBIOTA AND THINKING 

3045
02:40:29,800 --> 02:40:32,000
ABOUT PROBIOTIC THERAPIES AND I 

3046
02:40:32,000 --> 02:40:33,840
WANTING TO THROUGH OUR DATA 

3047
02:40:33,840 --> 02:40:37,360
USING SIN THEYING BIOLOGY TO 

3048
02:40:37,360 --> 02:40:39,120
ATTEMPT TO CONTROL ENGRAFTMENT 

3049
02:40:39,120 --> 02:40:46,160
OF A SINGLE MICROBE WHEN 

3050
02:40:46,160 --> 02:40:49,480
ENGRAFTED TO DIFFERENT 

3051
02:40:49,480 --> 02:40:49,840
MICROBIOTAS. 

3052
02:40:49,840 --> 02:40:53,760
MOST OF THE DATA I'LL PRESENT 

3053
02:40:53,760 --> 02:40:56,600
TODAY WAS DEVELOPED GENERATED IN

3054
02:40:56,600 --> 02:41:05,800
MY LAB BUT LICENSED BY NOVEME. 

3055
02:41:05,800 --> 02:41:12,760
I WANT TO START OFF WITH THEIR 

3056
02:41:12,760 --> 02:41:14,080
WONDERFUL WORK BUT THEY'RE 

3057
02:41:14,080 --> 02:41:15,360
INCREDIBLE SCIENTISTS THAT 

3058
02:41:15,360 --> 02:41:16,640
STARTED THIS COMPANY. 

3059
02:41:16,640 --> 02:41:21,760
I'M COFOUNDER THERE, ARE A FEW 

3060
02:41:21,760 --> 02:41:22,800
COFOUNDERS, I'M MOSTLY DOING 

3061
02:41:22,800 --> 02:41:25,560
WHAT I DID IN THE LAB WATCHING 

3062
02:41:25,560 --> 02:41:27,560
THEM DO AMAZING THINGS SO 

3063
02:41:27,560 --> 02:41:31,760
THEY'RE SYNTHETIC BIOLOGISTS AND

3064
02:41:31,760 --> 02:41:34,600
HAD THIS BEAUTIFUL VISION OF 

3065
02:41:34,600 --> 02:41:37,080
USING GUT MICROBES IN A WAY 

3066
02:41:37,080 --> 02:41:38,960
THAT'S DIFFERENT FROM THINKING 

3067
02:41:38,960 --> 02:41:41,560
ABOUT THEM AS OUR COMPOSITE 

3068
02:41:41,560 --> 02:41:43,680
BIOLOGY, USING THE SENSING 

3069
02:41:43,680 --> 02:41:45,320
CAPABILITIES OF THESE MAY BE 

3070
02:41:45,320 --> 02:41:46,760
ROBES THAT THEY'VE EVOLVED FOR 

3071
02:41:46,760 --> 02:41:49,360
THEIR SURVIVAL AND REWIRING THE 

3072
02:41:49,360 --> 02:41:52,360
SYSTEMS TO ALLOW THE MICROBES TO

3073
02:41:52,360 --> 02:41:54,960
MAKE DECISIONS, EXECUTE SPECIFIC

3074
02:41:54,960 --> 02:41:56,960
TASKS WITHIN THE GUT SO THINKING

3075
02:41:56,960 --> 02:41:59,640
ABOUT THE HUMAN MICROBIOTA IS A 

3076
02:41:59,640 --> 02:42:01,120
TECHNOLOGY PLATFORM FOR 

3077
02:42:01,120 --> 02:42:02,480
MANIPULATING HUMAN BIOLOGY. 

3078
02:42:02,480 --> 02:42:05,240
SO JUST TO REVIEW I THINK THERE 

3079
02:42:05,240 --> 02:42:07,880
ARE MANY DIFFERENT DEFINITIONS 

3080
02:42:07,880 --> 02:42:11,800
OF SYNTHETIC BIOLOGY. 

3081
02:42:11,800 --> 02:42:23,440
WE CAN THINK ABOUT NOTOBIOTIC 

3082
02:42:23,440 --> 02:42:23,800
MICE. 

3083
02:42:23,800 --> 02:42:25,920
SO WES HAMMERED HOME THIS IDEA 

3084
02:42:25,920 --> 02:42:28,520
OF GENERATING A PARTS LIST OF 

3085
02:42:28,520 --> 02:42:29,680
GENETIC PARTS THAT COULD BE 

3086
02:42:29,680 --> 02:42:33,120
WIRED TOGETHER IN DEVICES THAT 

3087
02:42:33,120 --> 02:42:34,680
WOULD GIVE PREDICTABLE OUTCOMES 

3088
02:42:34,680 --> 02:42:37,240
SO WE WORKED ON THIS VERY HARD 

3089
02:42:37,240 --> 02:42:41,000
FOR SEVERAL YEARS, FOCUSSED 

3090
02:42:41,000 --> 02:42:47,960
MAINLY ON THE BACK DROIDZ 

3091
02:42:47,960 --> 02:42:49,680
[PHONETIC SPELLING], AND I'LL 

3092
02:42:49,680 --> 02:42:53,280
SKIP A LOT OF THE BACKGROUND OF 

3093
02:42:53,280 --> 02:42:53,760
THIS. 

3094
02:42:53,760 --> 02:42:57,320
THE IMPORTANT HURDLE I WANT TO 

3095
02:42:57,320 --> 02:43:05,680
TALK ABOUT TODAY IS IS ISO GENIC

3096
02:43:05,680 --> 02:43:07,960
VISCOSITY IN THE GUT, PUBLISHED 

3097
02:43:07,960 --> 02:43:10,520
2013 IN NATURE THEY SHOWED IN 

3098
02:43:10,520 --> 02:43:19,920
YOU COLONIZE NOTBIOTIC MICE A 

3099
02:43:19,920 --> 02:43:21,880
SECOND MARKED STRAIN DIFFERENT 

3100
02:43:21,880 --> 02:43:23,920
FROM THE FIRST STRAIN CAN'T 

3101
02:43:23,920 --> 02:43:40,440
ENGRAFT IN THE MICROBIOTA. 

3102
02:43:40,440 --> 02:43:40,680
BIOTIC. 

3103
02:43:40,680 --> 02:43:44,760
>> SO WE, THIS CONCEPT OF ISO 

3104
02:43:44,760 --> 02:43:48,440
GENIC PRIORITY EXCLUSION IS ONE 

3105
02:43:48,440 --> 02:43:50,760
THAT HASN'T BEEN CONFINED TO THE

3106
02:43:50,760 --> 02:43:51,880
BACK TROIDZ. 

3107
02:43:51,880 --> 02:43:55,680
THERE'S A NICE STUDY OF WALTERS 

3108
02:43:55,680 --> 02:43:58,680
LAB LOOKING AT BIFIDA BACTERIA 

3109
02:43:58,680 --> 02:44:01,960
IN HUMANS AND THEY ADMINISTERED 

3110
02:44:01,960 --> 02:44:03,120
THIS PROBIOTIC FOR TWO WEEKS 

3111
02:44:03,120 --> 02:44:06,200
THAT SHOWS TYPE BY THE DENSITY 

3112
02:44:06,200 --> 02:44:07,760
OF THE MICROBE SURVEYED IN THE 

3113
02:44:07,760 --> 02:44:10,920
STOOL OF THESE INDIVIDUALS. 

3114
02:44:10,920 --> 02:44:14,640
ALL SHOW B LONG EM OVER TWO 

3115
02:44:14,640 --> 02:44:16,760
WEEKS AND ABOUT TWO THIRDS OF 

3116
02:44:16,760 --> 02:44:20,640
THEM CLEARED BIFIDA LONG EM THAT

3117
02:44:20,640 --> 02:44:23,320
WASHES OUT AFTER THE END OF THE 

3118
02:44:23,320 --> 02:44:25,200
TREATMENT BUT A THIRD OF THE 

3119
02:44:25,200 --> 02:44:30,920
GROUP AFTER TAKING B LONG EM HAS

3120
02:44:30,920 --> 02:44:36,680
APPEARS PERMANENTLY ENGRAFTED IN

3121
02:44:36,680 --> 02:44:42,520
THEIR BBIOOME AND HARBOR A 

3122
02:44:42,520 --> 02:44:44,600
SIMILAR STRAIN OF BASE LINE SO 

3123
02:44:44,600 --> 02:44:46,000
THE SAME EXCLUSION HAS BEEN 

3124
02:44:46,000 --> 02:44:49,760
SHOWN FOR A PATHOGEN FOR 

3125
02:44:49,760 --> 02:44:54,920
SALMONELLA BY DENISE'S LAB IN 

3126
02:44:54,920 --> 02:44:58,520
MICE MODEL SO THREE DIFFERENT 

3127
02:44:58,520 --> 02:45:00,360
YLA OF GUT BACTERIA. 

3128
02:45:00,360 --> 02:45:04,520
DOESN'T MEAN IT'S A UNIVERSAL 

3129
02:45:04,520 --> 02:45:05,400
PHENOMENON BUT SOMETHING THAEKS 

3130
02:45:05,400 --> 02:45:08,400
TENDS BEYOND THE BACK TROIDZ SO 

3131
02:45:08,400 --> 02:45:11,360
YOU KNOW I THINK IN THINKING 

3132
02:45:11,360 --> 02:45:15,840
ABOUT LAUNCHING A MICROBAL 

3133
02:45:15,840 --> 02:45:16,760
THERAPEUTIC COMPANY HOW DO YOU 

3134
02:45:16,760 --> 02:45:20,240
TAKE A STRAIN AND MAKE SURE IT 

3135
02:45:20,240 --> 02:45:23,320
WILL GRAFT REPRODUCIBLEY. 

3136
02:45:23,320 --> 02:45:24,720
WE HEARD TALKED ABOUT A KILL 

3137
02:45:24,720 --> 02:45:26,360
SWITCH THAT CAN YOU GET RID OF 

3138
02:45:26,360 --> 02:45:28,160
IT WHEN WANT TO SO THEY'VE BEEN 

3139
02:45:28,160 --> 02:45:29,760
DEVELOPING A LOT OF TOOLS FOR 

3140
02:45:29,760 --> 02:45:31,280
THIS BUT IT'S REALLY COMPLICATED

3141
02:45:31,280 --> 02:45:35,840
BY THE INDIVIDUALITY OF HUMAN 

3142
02:45:35,840 --> 02:45:40,840
MICROBIOTAS, SOME MAY HARBOR ISO

3143
02:45:40,840 --> 02:45:42,760
JENIC STRAINS SOME NOT SO LIZ 

3144
02:45:42,760 --> 02:45:45,000
LOOKED AT THREE DIFFERENT GROUPS

3145
02:45:45,000 --> 02:45:49,400
OF MICE ONE HARBORING A 

3146
02:45:49,400 --> 02:45:53,680
CONVENTIONING A MOUSE 

3147
02:45:53,680 --> 02:45:54,000
MICROBIOTA. 

3148
02:45:54,000 --> 02:45:56,920
SHE ADMINISTERED A SURROGATE 

3149
02:45:56,920 --> 02:45:59,280
THERAPEUTIC STRAIN A BACK TROIDZ

3150
02:45:59,280 --> 02:46:01,160
STRAIN THAT WAS LABELED IN 

3151
02:46:01,160 --> 02:46:04,520
EXPRESS IN GFP THAT WE CAN TRACK

3152
02:46:04,520 --> 02:46:06,440
AND SHE SHOWED THAT THE DENSITY 

3153
02:46:06,440 --> 02:46:08,520
OF THIS STRAIN OVER THE FIRST 

3154
02:46:08,520 --> 02:46:09,720
WEEK IN THESE THREE DIFFERENT 

3155
02:46:09,720 --> 02:46:12,080
GROUPS OF MICE VARIES WIDELY. 

3156
02:46:12,080 --> 02:46:14,680
ONE GROUP THAT COLONIZES TO HIGH

3157
02:46:14,680 --> 02:46:17,000
LEVEL AND DWINDLES ANOTHER THAT 

3158
02:46:17,000 --> 02:46:18,400
COLONIZES TO INTERMEDIATE LEVELS

3159
02:46:18,400 --> 02:46:20,560
AND APPEARS TO STAY CONSTANT THE

3160
02:46:20,560 --> 02:46:23,800
FIRST WEEK AND ANOTHER GROUP BY 

3161
02:46:23,800 --> 02:46:30,520
DAY 7 THIS MICROBE IS DROPPED 

3162
02:46:30,520 --> 02:46:34,120
BELOW THE LEVEL OF DETECTION. 

3163
02:46:34,120 --> 02:46:39,560
WE THOUGHT FEEDING IMULIN SO 

3164
02:46:39,560 --> 02:46:42,960
LET'S PROVIDE A SUPPORTING 

3165
02:46:42,960 --> 02:46:45,960
CARBOHYDRATE TO HELP IT. 

3166
02:46:45,960 --> 02:46:52,960
WHEN WE DISTRIBUTED IMULIN ONE 

3167
02:46:52,960 --> 02:46:58,280
OF THE GROUPS WASN'T DURABLE IT 

3168
02:46:58,280 --> 02:47:00,520
DIDN'T COME BACK FROM DETEST. 

3169
02:47:00,520 --> 02:47:02,400
THIS STRAIN WE ORIGINALLY 

3170
02:47:02,400 --> 02:47:04,480
ISOLATED FOR ABILITY TO UTILIZE 

3171
02:47:04,480 --> 02:47:09,040
A SOMEWHAT UNIQUE POLY SACK RIDE

3172
02:47:09,040 --> 02:47:25,640
IN THE DIET KNOWN AS PORFORIN SO

3173
02:47:25,640 --> 02:47:30,160
FEEDING SEAWEED WE SEE HIGH AND 

3174
02:47:30,160 --> 02:47:31,120
PRE-PRODUCIBLE LEVELS ACHIEVED 

3175
02:47:31,120 --> 02:47:32,040
INDEPENDENT OF THE BACKGROUND 

3176
02:47:32,040 --> 02:47:33,680
GUT MICROBIOTA SO THIS 

3177
02:47:33,680 --> 02:47:37,360
PRIVILEGED ACCESS TO POLY AGO 

3178
02:47:37,360 --> 02:47:39,720
RIDE WHERE THERE'S NO BACKGROUND

3179
02:47:39,720 --> 02:47:41,360
COMPETITION WE KNOW THERE'S 

3180
02:47:41,360 --> 02:47:42,880
PROBABLY DIFFERENT LEVELS OF 

3181
02:47:42,880 --> 02:47:48,880
COMPETITION FOR IMULIN BUT 

3182
02:47:48,880 --> 02:47:50,560
PORFORIN ALLOWS THE THERAPEUTIC 

3183
02:47:50,560 --> 02:47:58,960
STRAIN TO BLOOM PROCEED 

3184
02:47:58,960 --> 02:48:01,880
PRODUCEABLELY. 

3185
02:48:01,880 --> 02:48:07,160
THEY GAVE THE ABILITY TO ABILITY

3186
02:48:07,160 --> 02:48:10,320
TO POLY SACK RIDE OUT I WILL 

3187
02:48:10,320 --> 02:48:11,760
SAYINGS AND THEY SHOW LOOKING AT

3188
02:48:11,760 --> 02:48:14,160
THE DENTIST OF THAT ENGINEERED 

3189
02:48:14,160 --> 02:48:16,400
STRAIN THEY CAN TOGGLE THE 

3190
02:48:16,400 --> 02:48:18,520
ABUNDANCE OF THE STRAIN, SO GO 

3191
02:48:18,520 --> 02:48:20,520
FROM LOW TO HIGH LEVELS WHEN 

3192
02:48:20,520 --> 02:48:25,640
THEY FEED PORFORIN IN COMPARISON

3193
02:48:25,640 --> 02:48:28,000
TO TOTAL CULTURE DENSITY HERE SO

3194
02:48:28,000 --> 02:48:29,880
THEY THINK THEY'RE ACHIEVING 10 

3195
02:48:29,880 --> 02:48:32,720
PERCENT OF THE DENSITY OF THE 

3196
02:48:32,720 --> 02:48:34,680
MICROBIOTA ON HIGH DOSE SEAWEED 

3197
02:48:34,680 --> 02:48:35,200
EXTRACT. 

3198
02:48:35,200 --> 02:48:37,360
THEY TAKE THE SEAWEED AWAY THE 

3199
02:48:37,360 --> 02:48:39,080
STRAIN DROPS TO A LOWER LEVEL. 

3200
02:48:39,080 --> 02:48:41,160
THEY ALSO SHOWED THAT THIS IS 

3201
02:48:41,160 --> 02:48:44,880
DOSE RESPONSIVE SO AT 1 PERCENT 

3202
02:48:44,880 --> 02:48:48,000
PORFORIN THEY ACHIEVED TEN TO 

3203
02:48:48,000 --> 02:48:54,640
THE 10th CFU PER MILL. 

3204
02:48:54,640 --> 02:48:57,600
SO NOT EXACTLY WHAT I WOULD HAVE

3205
02:48:57,600 --> 02:48:59,040
PREDICTED A DIRECT LYNN REGARD 

3206
02:48:59,040 --> 02:49:03,360
RELATIONSHIP OF THE PORFORIN IN 

3207
02:49:03,360 --> 02:49:05,200
THE DIET COMPARED TO THE DENSITY

3208
02:49:05,200 --> 02:49:07,400
OF MICROBE IN THE GUT. 

3209
02:49:07,400 --> 02:49:09,680
WE CAN STAIN THOSE BACKGROUND 

3210
02:49:09,680 --> 02:49:11,720
MICROBES IN PINK HERE AND OUR 

3211
02:49:11,720 --> 02:49:13,520
STRAIN IN GREEN ON LOW DOSE HIGH

3212
02:49:13,520 --> 02:49:17,080
DOSE PORFORIN YOU CAN SEE MANY 

3213
02:49:17,080 --> 02:49:18,760
OF THE BACK TROIDZ IN THE HIGH 

3214
02:49:18,760 --> 02:49:20,960
DOSE PORFORIN. 

3215
02:49:20,960 --> 02:49:25,880
ONE INTERESTING NOTE HERE IS 

3216
02:49:25,880 --> 02:49:27,960
OTHER THINGS HAPPENING BESIDES 

3217
02:49:27,960 --> 02:49:29,200
ENGRAFTMENT OF THE STRAIN. 

3218
02:49:29,200 --> 02:49:33,360
TWO ISO GENIC STRAINS OF BACK 

3219
02:49:33,360 --> 02:50:03,320
TROIDZ ONE. 

3220
02:50:03,320 --> 02:50:05,320
>> THE FIRST STRAIN HAS BEEN 

3221
02:50:05,320 --> 02:50:08,200
ELIMINATED FROM THE MICROBIOTA. 

3222
02:50:08,200 --> 02:50:09,840
REALLY, ILLUMINATING EXPERIMENT 

3223
02:50:09,840 --> 02:50:12,000
HERE WAS ONE THAT ACTUALLY WAS 

3224
02:50:12,000 --> 02:50:13,760
CAUSED BY A SCHEDULING CONFLICT 

3225
02:50:13,760 --> 02:50:15,920
WHERE LIZ HAD TO DO THE 

3226
02:50:15,920 --> 02:50:18,760
PORPHORIN FEEDING FOR A SHORTER 

3227
02:50:18,760 --> 02:50:20,760
PERIOD OF TIME. 

3228
02:50:20,760 --> 02:50:22,520
LEAVE THESE LUCKY RESULTS WHERE 

3229
02:50:22,520 --> 02:50:24,400
WHEN YOU FEED FOR A SHORTER TIME

3230
02:50:24,400 --> 02:50:26,080
YOU START TO SEE DISAPPEARANCE 

3231
02:50:26,080 --> 02:50:33,120
OF THE FIRST COME  -- COLONIZER.

3232
02:50:33,120 --> 02:50:35,400
WHEN YOU STOP THE PORPHORIN THE 

3233
02:50:35,400 --> 02:50:38,440
FIRST STRAIN THAT CANNOT USE IT 

3234
02:50:38,440 --> 02:50:40,960
BOUNCES BACK AND EXHIBITED EQUAL

3235
02:50:40,960 --> 02:50:42,960
ABUNDANCE IN THE ABSENCE TO A 

3236
02:50:42,960 --> 02:50:45,520
I-ING STRAIN SO THERE APPEARS TO

3237
02:50:45,520 --> 02:50:47,240
BE AN EXCHANGE PROCESS THAT DOES

3238
02:50:47,240 --> 02:50:49,560
NOT GO TO COMPLETION ON THE 

3239
02:50:49,560 --> 02:50:52,960
SHORTER DURATION PORPHORIN 

3240
02:50:52,960 --> 02:50:53,600
FEEDING. 

3241
02:50:53,600 --> 02:50:56,320
INTO IT APPEARS THIS HAS TO DO 

3242
02:50:56,320 --> 02:50:58,480
WITH CRYPT LOCALIZATION SO BASED

3243
02:50:58,480 --> 02:51:04,320
ON FINDINGS FROM THE MASMANIAN 

3244
02:51:04,320 --> 02:51:08,600
THAT INDICATED THAT CRYPT 

3245
02:51:08,600 --> 02:51:10,520
LOCALIZATION WAS IMPORTANT, WE 

3246
02:51:10,520 --> 02:51:12,280
LOOKED AT THE FIRST ARRIVING 

3247
02:51:12,280 --> 02:51:13,320
STRAIN FIRST IN RECOMMENDED 

3248
02:51:13,320 --> 02:51:16,520
SECOND IN GREEN IN THE SKIES OF 

3249
02:51:16,520 --> 02:51:20,120
ISO GENIC EXCLUSION WE SEE 

3250
02:51:20,120 --> 02:51:22,120
EXCHANGE BUT AS THE EXCHANGE 

3251
02:51:22,120 --> 02:51:25,240
HAPPENS WE SEE THE SECOND 

3252
02:51:25,240 --> 02:51:30,040
ARRIVING PORPHORIN GREEN STRAIN 

3253
02:51:30,040 --> 02:51:38,080
INVADE THE CRYPTS. 

3254
02:51:38,080 --> 02:51:43,680
SO NOW, NOVOME HAS TAKEN TO 

3255
02:51:43,680 --> 02:51:45,320
CLINICAL TRIALS IN HUMANS AND 

3256
02:51:45,320 --> 02:51:47,840
HERE WE SEE INDIVIDUALS THAT ARE

3257
02:51:47,840 --> 02:51:49,880
SEEING PORPHORIN UTILIZE'S 

3258
02:51:49,880 --> 02:51:51,840
STRAIN RECEIVING EITHER NO 

3259
02:51:51,840 --> 02:51:54,720
PORPHORIN OR INCREASING DOSES OF

3260
02:51:54,720 --> 02:51:56,160
PORPHORIN AND BASICALLY WE SEE 

3261
02:51:56,160 --> 02:51:59,040
THE SAME AS IN THE MOUSE MODEL 

3262
02:51:59,040 --> 02:52:02,000
INCREASING LEVELS MUCH DENSITY 

3263
02:52:02,000 --> 02:52:03,840
OF THE PORPHORIN UTILIZING 

3264
02:52:03,840 --> 02:52:05,560
STRAIN AND HIGHEST DENSITY 

3265
02:52:05,560 --> 02:52:08,840
ACHIEVED IN THE HIGHEST DOSE 

3266
02:52:08,840 --> 02:52:10,360
PORPHORIN AND THIS IS AN 

3267
02:52:10,360 --> 02:52:11,200
ATTENUATED STRAIN WITH KILL 

3268
02:52:11,200 --> 02:52:13,800
SWITCH SO YOU REMOVE THE 

3269
02:52:13,800 --> 02:52:14,760
PORPHORIN THESE STRAINS CRASHED 

3270
02:52:14,760 --> 02:52:18,000
OUT OF THE MICROBIOTA AND WASHED

3271
02:52:18,000 --> 02:52:20,040
OUT SO NOW THEY'RE MOVING ON TO 

3272
02:52:20,040 --> 02:52:24,640
PHASE 2-A WITH HIGH DOSE A THAN 

3273
02:52:24,640 --> 02:52:28,320
STRAIN THAT DEGENERATES TO DEAL 

3274
02:52:28,320 --> 02:52:37,680
WITH HYPER OXILREA I WANT TO 

3275
02:52:37,680 --> 02:52:40,960
FINISH WITH HUMAN STUDDISTS THAT

3276
02:52:40,960 --> 02:52:42,960
CHANGE HOST BIOLOGY PARAMETERS 

3277
02:52:42,960 --> 02:52:45,720
WITH DIET INDUCED AL TRAIGSZ, 

3278
02:52:45,720 --> 02:52:48,320
THIS IS THE RESULT OF A CENTER 

3279
02:52:48,320 --> 02:52:53,360
FOR HUMAN MICROBIOME STUDIES, 

3280
02:52:53,360 --> 02:52:56,760
CHRISTOPHER GARDNER HAS BEEN 

3281
02:52:56,760 --> 02:53:03,160
PERFORMING DIETARY STUDIES WE 

3282
02:53:03,160 --> 02:53:09,520
SEE THE FEE FFI-FO STUDY IN 

3283
02:53:09,520 --> 02:53:10,960
COLLABORATION WITH CHRISTOPHER'S

3284
02:53:10,960 --> 02:53:13,280
GROUP FIBER AN FUR MEANTED AND 

3285
02:53:13,280 --> 02:53:21,160
LOOKING AT KETOGENIC DIETARY 

3286
02:53:21,160 --> 02:53:23,120
INTERVENTIONS BUT ALSO 

3287
02:53:23,120 --> 02:53:34,160
PROBIOTICS AND PRO  -- 

3288
02:53:34,160 --> 02:53:34,520
PRE-BIOTICS.  

3289
02:53:34,520 --> 02:53:36,240
>> WE ARE LOOKING AT THE 

3290
02:53:36,240 --> 02:53:37,720
PARAMETERS ASSOCIATED WITH 

3291
02:53:37,720 --> 02:53:39,320
METABOLIC SYNDROME, THIS IS AN 

3292
02:53:39,320 --> 02:53:40,560
PROBIOTIC WITH THREE STRAINS 

3293
02:53:40,560 --> 02:53:43,440
THAT HAVE EVIDENCE FOR IMPACT OF

3294
02:53:43,440 --> 02:53:45,880
FEATURES OF METABOLIC SYNDROME. 

3295
02:53:45,880 --> 02:53:49,360
WE HAVE A PLACEBO CONTROLLED 

3296
02:53:49,360 --> 02:53:51,920
TRIAL BASELINE TEN WEEK 

3297
02:53:51,920 --> 02:53:53,200
INTERVENTION AND WASHOUT PERIOD 

3298
02:53:53,200 --> 02:53:55,360
WHERE WE TAKE STOOL AND BLOOD 

3299
02:53:55,360 --> 02:53:58,200
AND MEASURING THINGS AS WELL AS 

3300
02:53:58,200 --> 02:54:00,120
CONDUCTING FOOD SURVEYS. 

3301
02:54:00,120 --> 02:54:04,520
QUICK SUMMARY RESULTS, NO COHORT

3302
02:54:04,520 --> 02:54:07,000
WIDE EFFECTS ON METABOLIC 

3303
02:54:07,000 --> 02:54:08,760
SYNDROME OR NO ENGRAFTMENT OF 

3304
02:54:08,760 --> 02:54:11,080
THESE METABOLIC STRAINS BUT 

3305
02:54:11,080 --> 02:54:12,080
THERE APPEAR TO BE INTERACTION 

3306
02:54:12,080 --> 02:54:14,240
WITH FACET OF DIET AND THERE'S A

3307
02:54:14,240 --> 02:54:16,760
SUBSET OF INTERVENTION GROUP 

3308
02:54:16,760 --> 02:54:18,800
THAT RESPONDS BASED ON WHAT 

3309
02:54:18,800 --> 02:54:22,080
THEY'RE EATING OR CORRESPONDING 

3310
02:54:22,080 --> 02:54:25,120
TO THAT SO WE WILL REPORT THAT 

3311
02:54:25,120 --> 02:54:25,320
SOON. 

3312
02:54:25,320 --> 02:54:27,560
>> YOU HAVE ABOUT ONE MINUTE. 

3313
02:54:27,560 --> 02:54:28,640
>> YOU HAVE ONE MINUTE. 

3314
02:54:28,640 --> 02:54:30,280
>> PERFECT. 

3315
02:54:30,280 --> 02:54:32,280
LAST SLIDE. 

3316
02:54:32,280 --> 02:54:35,280
WE HAVE ALSO CONDUCTED A 

3317
02:54:35,280 --> 02:54:38,040
PRE-BIOTIC STUDY FOR RE-JUVE 

3318
02:54:38,040 --> 02:54:41,240
NATION OF THE AGING MICROBIOTA 

3319
02:54:41,240 --> 02:54:43,840
AND LOOKING AT THE POSSIBILITY 

3320
02:54:43,840 --> 02:54:51,160
OF A MILK SACK RIDE, TWO FUCOSYL

3321
02:54:51,160 --> 02:54:53,880
LACK TOE METABOLIC MARKERS 

3322
02:54:53,880 --> 02:54:56,560
PLACEBO CONTROLLED WITH LOW DOSE

3323
02:54:56,560 --> 02:54:57,920
HIGH DOSE AND BASELINE PERIOD IN

3324
02:54:57,920 --> 02:55:00,160
THIS CASE I THINK WE HAVE A SIX 

3325
02:55:00,160 --> 02:55:03,240
WEEK INTERVENTION AND A WASHOUT 

3326
02:55:03,240 --> 02:55:08,000
AND WE DO SEE A DOSE CAN 

3327
02:55:08,000 --> 02:55:11,160
DEPENDENT BLOOM IN BIFIDA TRIAL.

3328
02:55:11,160 --> 02:55:12,880
I WANT TO END BY ACKNOWLEDGEING 

3329
02:55:12,880 --> 02:55:13,840
THE WONDERFUL PEOPLE IN MY 

3330
02:55:13,840 --> 02:55:15,000
GROUP. 

3331
02:55:15,000 --> 02:55:16,320
I THINK I MENTIONED THE MAIN 

3332
02:55:16,320 --> 02:55:18,160
ONES DURING THE TALK, MANY 

3333
02:55:18,160 --> 02:55:20,360
WONDERFUL COLLABORATORS, THANKS 

3334
02:55:20,360 --> 02:55:23,120
TO OUR FUNDING SOURCES INCLUDING

3335
02:55:23,120 --> 02:55:26,160
NCCIH AND NIDDK AND THANKS VERY 

3336
02:55:26,160 --> 02:55:26,520
MUCH. 

3337
02:55:26,520 --> 02:55:29,840
I'M EAGER TO HEAR THE REST OF 

3338
02:55:29,840 --> 02:55:34,200
THE TALKS. 

3339
02:55:34,200 --> 02:55:36,400
>> THANK YOU VERY MUCH, 

3340
02:55:36,400 --> 02:55:37,760
DR. SONNENBURG. 

3341
02:55:37,760 --> 02:55:41,840
OUR NEXT SPEAKER IS DR. KASHYAP 

3342
02:55:41,840 --> 02:55:50,240
FROM ROCHESTER CLINIC THE ROAD 

3343
02:55:50,240 --> 02:55:54,240
TO MICROBIAL DRIVEN MEDICINE. 

3344
02:55:54,240 --> 02:55:59,160
>> THANK YOU FOR INVITING ME. 

3345
02:55:59,160 --> 02:56:06,760
I WANT TO TALK A LITTLE BIT 

3346
02:56:06,760 --> 02:56:08,760
MICROBUY OL FITS IN SYSTEMS 

3347
02:56:08,760 --> 02:56:10,960
BIOLOGY IN TERMS OF DRIVING THE 

3348
02:56:10,960 --> 02:56:13,640
SELECTION OF PRECISION OF 

3349
02:56:13,640 --> 02:56:13,960
PROBIOTICS. 

3350
02:56:13,960 --> 02:56:15,760
SCLOESH SUR NOT RESULT OF THE 

3351
02:56:15,760 --> 02:56:16,240
TOPIC TODAY. 

3352
02:56:16,240 --> 02:56:22,120
I START WITH A CODE QUOTE FROM 

3353
02:56:22,120 --> 02:56:26,240
WILLIAM . . .  WE TRY TO THINK 

3354
02:56:26,240 --> 02:56:28,320
ABOUT IT AS SCIENCE BUT IT'S 

3355
02:56:28,320 --> 02:56:30,560
PRACTICED AS ART WAS TREATMENT 

3356
02:56:30,560 --> 02:56:32,520
IS DEVELOPED AS ONE SIZE FITS 

3357
02:56:32,520 --> 02:56:35,280
ALL AND PHYSICIANS ARE LEFT WITH

3358
02:56:35,280 --> 02:56:36,280
INDIVIDUALIZED TREATMENT BASED 

3359
02:56:36,280 --> 02:56:37,640
ON EXPERIENCE WITH PATIENTS. 

3360
02:56:37,640 --> 02:56:39,760
AS WE THINK ABOUT PRECISION 

3361
02:56:39,760 --> 02:56:41,080
MEDICINE IS TRYING TO CHANGE 

3362
02:56:41,080 --> 02:56:43,840
THAT A MODEL WHEREBY EACH 

3363
02:56:43,840 --> 02:56:45,800
TREATMENT IS GOING TO BE 

3364
02:56:45,800 --> 02:56:46,520
TAILORED TO AN INDIVIDUAL 

3365
02:56:46,520 --> 02:56:49,000
PATIENT INSTEAD OF USING ONE 

3366
02:56:49,000 --> 02:56:52,360
SIZE FITS ALL AND DONE BY 

3367
02:56:52,360 --> 02:56:53,400
COMBINING DIFFERENT DATA. 

3368
02:56:53,400 --> 02:56:57,360
OF COURSE, I THINK FAR OFF BEING

3369
02:56:57,360 --> 02:56:59,120
ABLE TO DEVELOP TREATMENTS FOR 

3370
02:56:59,120 --> 02:57:00,840
INDIVIDUALS WE THINK ABOUT 

3371
02:57:00,840 --> 02:57:02,520
PUTTING THEM INTO SMALLER 

3372
02:57:02,520 --> 02:57:03,760
SUBGROUPS WHICH RIGHT NOW ARE 

3373
02:57:03,760 --> 02:57:06,640
JUST RELYING ON CLINICAL 

3374
02:57:06,640 --> 02:57:08,960
LABORATORY DATA BUT HOPEFULLY AS

3375
02:57:08,960 --> 02:57:12,760
WE MOVE FORWARD ESPECIALLY WITH 

3376
02:57:12,760 --> 02:57:15,960
PRECISION BIOTICS WILL WILL BE 

3377
02:57:15,960 --> 02:57:20,600
BASED ON SOME FORM OF 

3378
02:57:20,600 --> 02:57:25,680
MICROBIOLOGIC

3379
02:57:25,680 --> 02:57:26,080
MICROBIOLOGICAL. 

3380
02:57:26,080 --> 02:57:29,160
>> WE STARTED ADDING THE HOST 

3381
02:57:29,160 --> 02:57:30,520
GENOME AND THOUGHT WE WILL BE 

3382
02:57:30,520 --> 02:57:33,120
ABLE TO FIND THE ANSWER TO MOST 

3383
02:57:33,120 --> 02:57:33,400
DISEASES. 

3384
02:57:33,400 --> 02:57:35,960
WE ARE FAR FROM THAT HAND SLOWLY

3385
02:57:35,960 --> 02:57:38,520
REALIZING THERE MIGHT BE SOME 

3386
02:57:38,520 --> 02:58:01,480
DISEASES WHICH ARE PREDOMINANTLY

3387
02:58:01,480 --> 02:58:01,760
MICROOBAMA. 

3388
02:58:01,760 --> 02:58:03,640
>> IF YOU LOOK AT SUBGROUPS IN 

3389
02:58:03,640 --> 02:58:05,640
EACH DISEASE THERE MIGHT BE A 

3390
02:58:05,640 --> 02:58:07,000
STRONG COMPONENT AND THAT'S 

3391
02:58:07,000 --> 02:58:08,840
WHERE PRECISION MEDICINE COMES 

3392
02:58:08,840 --> 02:58:09,360
IN. 

3393
02:58:09,360 --> 02:58:10,600
WHEN YOU THINK ABOUT DIFFERENT 

3394
02:58:10,600 --> 02:58:12,640
COMPONENTS THEY DON'T LIVE IN A 

3395
02:58:12,640 --> 02:58:14,680
VACUUM SO THEY NEED TO BE TAKEN 

3396
02:58:14,680 --> 02:58:16,320
TOGETHER INTO ACCOUNT.

3397
02:58:16,320 --> 02:58:20,360
WHEN WE STUDY ONLY AN EXPOSED 

3398
02:58:20,360 --> 02:58:22,160
BIOME OR THE HOST WE MAY BE 

3399
02:58:22,160 --> 02:58:24,240
ATTRIBUTING A LOT MORE THAN THAT

3400
02:58:24,240 --> 02:58:28,160
ONE FACTOR AS OSTER MAN TAKING 

3401
02:58:28,160 --> 02:58:29,040
ALL TOGETHER. 

3402
02:58:29,040 --> 02:58:32,720
SO IF YOU WERE TO CONSIDER 

3403
02:58:32,720 --> 02:58:34,160
COMBINING SOME OF THESE DATA 

3404
02:58:34,160 --> 02:58:37,320
ADVANTAGE BY INTEGRATION USING 

3405
02:58:37,320 --> 02:58:38,720
UNBIASED METHODS WE COULD 

3406
02:58:38,720 --> 02:58:43,920
DEVELOP MODELS BASED ON A. I. 

3407
02:58:43,920 --> 02:58:46,320
AND A GOOD EXAMPLE OF THIS IS 

3408
02:58:46,320 --> 02:58:49,680
RESPONSE TO DIET IN CHANGES OF 

3409
02:58:49,680 --> 02:58:51,960
BLOOD GLUCOSE OR LIP IDZ BUT 

3410
02:58:51,960 --> 02:58:57,200
THESE STUDIES PROVIDE INSIGHT 

3411
02:58:57,200 --> 02:59:02,040
CELL CULTURE AND TOGETHER THE 

3412
02:59:02,040 --> 02:59:02,960
MECHANISMS IN IDENTIFICATION OF 

3413
02:59:02,960 --> 02:59:05,640
NOVEL TARGETS AND IN FACT, THIS 

3414
02:59:05,640 --> 02:59:07,440
CAN THEN BE VALIDATED BACK IN 

3415
02:59:07,440 --> 02:59:11,760
HUMAN STUDIES TO SEE IF 

3416
02:59:11,760 --> 02:59:13,720
MECHANISMS WHICH CAME OUT OF 

3417
02:59:13,720 --> 02:59:15,320
PRE-CLINICAL MODELS HOLD TRUE IN

3418
02:59:15,320 --> 02:59:17,160
HUMAN STUDIES BUT MORE 

3419
02:59:17,160 --> 02:59:22,440
IMPORTANTLY THIS WILL HOPEFULLY 

3420
02:59:22,440 --> 02:59:25,560
PROVIDE A BETTER WAY FOR 

3421
02:59:25,560 --> 02:59:27,080
PRECISION PROBIOTICS IN THE 

3422
02:59:27,080 --> 02:59:27,320
FUTURE. 

3423
02:59:27,320 --> 02:59:31,400
I WANT TO FOCUS ON A DEAL, 

3424
02:59:31,400 --> 02:59:33,520
IRRITABLE BOWEL SYNDROME AND WE 

3425
02:59:33,520 --> 02:59:35,840
KNOW THAT BOTH DIET AND MICROBES

3426
02:59:35,840 --> 02:59:37,920
ARE AN IMPORTANT PART OF THE 

3427
02:59:37,920 --> 02:59:38,280
PHYSIOLOGY. 

3428
02:59:38,280 --> 02:59:41,240
IT'S A SYMPTOM BASED DISEASE 

3429
02:59:41,240 --> 02:59:44,640
CLASSIFIED BASED ON ABDOMINAL 

3430
02:59:44,640 --> 02:59:46,280
PAIN WHICH COULD BE ASSOCIATED 

3431
02:59:46,280 --> 02:59:48,240
WITH CHANGES IN DEFACATION IN 

3432
02:59:48,240 --> 02:59:50,760
FREQUENCY OF STOOL OR APPEARANCE

3433
02:59:50,760 --> 02:59:55,520
OF STOOL AND DECLASSIFIED AS 

3434
02:59:55,520 --> 02:59:58,240
CONSTIPATION, DIET PREDOMINANT 

3435
02:59:58,240 --> 03:00:02,200
OR MIXED FORM. 

3436
03:00:02,200 --> 03:00:05,280
THE FACTORS ASSOCIATED WITH IBS 

3437
03:00:05,280 --> 03:00:07,680
ARE ALL FACTORS WHICH CAN AFFECT

3438
03:00:07,680 --> 03:00:10,080
THE MICROBIOME AND THE 

3439
03:00:10,080 --> 03:00:12,520
UNDERLYING PATH OL OF IBS 

3440
03:00:12,520 --> 03:00:27,200
INCLUDING CHANGES OF TRANSIT SO 

3441
03:00:27,200 --> 03:00:29,720
WE DID A A STUDY OF THE DAD I'M 

3442
03:00:29,720 --> 03:00:31,120
GOING TO SHARE TODAY. 

3443
03:00:31,120 --> 03:00:32,360
I'M NOT GOING TO SHARE ALL THE 

3444
03:00:32,360 --> 03:00:35,440
DATA FROM THE STUDY BUT I WANT 

3445
03:00:35,440 --> 03:00:39,360
TO MAKE A FEW POINTS WITH THE 

3446
03:00:39,360 --> 03:00:40,520
STUDY. 

3447
03:00:40,520 --> 03:00:44,200
THIS WAS A STUDY IN OWN TWO 

3448
03:00:44,200 --> 03:00:45,960
PHENOTYPES WHERE WE COLLECTED A 

3449
03:00:45,960 --> 03:00:47,720
LOT OF THE HOST INFORMATION 

3450
03:00:47,720 --> 03:00:50,960
INCLUDING CLINICAL META DATA AS 

3451
03:00:50,960 --> 03:00:52,760
WELL AS ENVIRONMENTAL DATA DIE 

3452
03:00:52,760 --> 03:00:56,160
FRIDAY DATA EVERY TIME POINT, WE

3453
03:00:56,160 --> 03:00:58,880
COLLECTED STOOL SAMPLES IN SIX 

3454
03:00:58,880 --> 03:01:01,960
MONTHS, WE ALSO COLLECTED HOST 

3455
03:01:01,960 --> 03:01:04,960
SAMPLES IN FORM OF COLON 

3456
03:01:04,960 --> 03:01:06,480
BIOPSIES AND BLOOD AND THIS 

3457
03:01:06,480 --> 03:01:09,600
PROVIDED US WITH OPPORTUNITY TO 

3458
03:01:09,600 --> 03:01:15,920
LOOK AT EXTENSIVE LOOKS AT HOST 

3459
03:01:15,920 --> 03:01:17,080
AN MICROBES. 

3460
03:01:17,080 --> 03:01:26,400
I'VE OUTLINED EXCLUSION HERE WE 

3461
03:01:26,400 --> 03:01:29,160
TRY TO MATCH FOR AGE. 

3462
03:01:29,160 --> 03:01:31,000
WE LOOK AT THE DATA, FIRST 

3463
03:01:31,000 --> 03:01:33,440
DECIDED AS I MENTIONED THAT THIS

3464
03:01:33,440 --> 03:01:36,040
KIND OF MODEL CAN SERVE TO 

3465
03:01:36,040 --> 03:01:39,080
VALIDATE WHEN WE FOUND IN FETAL 

3466
03:01:39,080 --> 03:01:39,520
STUDIES. 

3467
03:01:39,520 --> 03:01:42,400
IF WE FOCUS ON SOME METHOD 

3468
03:01:42,400 --> 03:01:43,320
PREVIOUSLY IDENTIFIED THE FIRST 

3469
03:01:43,320 --> 03:01:43,840
TIME. 

3470
03:01:43,840 --> 03:01:49,240
A LOT OF EARLY WORK IN A LAB ON 

3471
03:01:49,240 --> 03:01:51,560
BACTERIAL FATTY ACID AND HOW 

3472
03:01:51,560 --> 03:01:54,960
THEY INFLUENCE SEROTONIN IN THE 

3473
03:01:54,960 --> 03:02:08,320
GUT WHAT WE FOUND IN OUR 

3474
03:02:08,320 --> 03:02:11,960
PATIENTS WHEN WE LOOKED AT THE 

3475
03:02:11,960 --> 03:02:20,000
STOOL SAMPLES DECREASED FROM 

3476
03:02:20,000 --> 03:02:23,960
PATIENTS WITH CONSTIPATION 

3477
03:02:23,960 --> 03:02:29,160
IRRITABLE BOWEL SYNDROME. 

3478
03:02:29,160 --> 03:02:32,200
BUT, WE FOUND THIS IS NOT AN 

3479
03:02:32,200 --> 03:02:33,040
INCIDENTAL FINDING. 

3480
03:02:33,040 --> 03:02:37,160
THE CHANGE PERSISTS OVER THE 6 

3481
03:02:37,160 --> 03:02:41,520
MONTHS THAT SAMPLED THESE 

3482
03:02:41,520 --> 03:02:41,760
PATIENTS. 

3483
03:02:41,760 --> 03:02:45,440
WE TOOK A STOOL SAMPLE TO SEE IF

3484
03:02:45,440 --> 03:02:53,360
THE TRANSITED PHENOTYPE CAN 

3485
03:02:53,360 --> 03:02:57,480
BE -- AND HAD A LONGER TRANSIT 

3486
03:02:57,480 --> 03:02:57,800
LINE. 

3487
03:02:57,800 --> 03:02:59,240
WE LOOKED FOR THE APPEARANCE OF 

3488
03:02:59,240 --> 03:03:01,840
THE DYE IN THE STOOL AND THAT 

3489
03:03:01,840 --> 03:03:04,240
GIVES US THE TRANSIT TIME IN THE

3490
03:03:04,240 --> 03:03:06,520
G. I. ATTRACT AND WE FOUND IT 

3491
03:03:06,520 --> 03:03:08,520
WAS SLOWER IN MICE AS COMPARED 

3492
03:03:08,520 --> 03:03:10,160
TO THE HEALTHY CONTROLS AND WE 

3493
03:03:10,160 --> 03:03:15,560
LOOKED AT THE FATTY ACID LEVELS 

3494
03:03:15,560 --> 03:03:17,360
AS COMPARED TO CONTROL. 

3495
03:03:17,360 --> 03:03:20,680
SO COMBINING WHAT WE HAD SEEN IN

3496
03:03:20,680 --> 03:03:23,880
PRE-CLINICAL MODELS IT PROVIDES 

3497
03:03:23,880 --> 03:03:27,720
FAIRLY STRONG EVIDENCE. 

3498
03:03:27,720 --> 03:03:30,760
THE NEXT QUESTION WHAT'S DRIVING

3499
03:03:30,760 --> 03:03:50,680
THE BU TRAIT PRODUCTION. 

3500
03:03:50,680 --> 03:03:53,200
WE THINK IT'S LIKELY DRIVEN BY 

3501
03:03:53,200 --> 03:03:55,760
THE MICROBE. 

3502
03:03:55,760 --> 03:03:59,200
SO WE LOOKED AT SPECIFIC 

3503
03:03:59,200 --> 03:04:02,720
BACTERIA GENOMIC REGIONS AND 

3504
03:04:02,720 --> 03:04:05,000
IDENTIFIED TWO GENE REGIONS IN 

3505
03:04:05,000 --> 03:04:08,760
OUR COHORT WHICH COORDINATED 

3506
03:04:08,760 --> 03:04:18,120
WITH THE BU TRAIT PRODUCTION. 

3507
03:04:18,120 --> 03:04:23,040
IF BU TRAIT IS A DRIVER IT 

3508
03:04:23,040 --> 03:04:25,200
SHOULD BE REDUCED IN PEOPLE WHO 

3509
03:04:25,200 --> 03:04:28,160
CONSUME A LOT OF FIBER BASELINE 

3510
03:04:28,160 --> 03:04:33,240
AND THEN REDUCE THE FIBER 

3511
03:04:33,240 --> 03:04:33,480
INTAKE. 

3512
03:04:33,480 --> 03:04:34,400
WE COULD SEE A SIGNIFICANT 

3513
03:04:34,400 --> 03:04:37,880
INCREASE IN THE FIBER WHICH 

3514
03:04:37,880 --> 03:04:40,840
COLLECTED SAMPLES BEFORE AND 

3515
03:04:40,840 --> 03:04:42,840
AFTER IN THE DIELT AS WELL AS 

3516
03:04:42,840 --> 03:04:43,120
SYMPTOMS. 

3517
03:04:43,120 --> 03:04:47,120
AS EXPECTED AS THE FIBER LEVELS 

3518
03:04:47,120 --> 03:04:51,160
DROP, THE FATTY ACID DROPS IN 

3519
03:04:51,160 --> 03:04:54,560
THE INTESTINE AND STOOL BUT 

3520
03:04:54,560 --> 03:04:56,200
THERE WAS DECREASE IN 

3521
03:04:56,200 --> 03:04:59,160
MICRODIVERSITY WHICH COORDINATED

3522
03:04:59,160 --> 03:05:03,200
WITH THE APPEARANCE OF SYMPTOMS 

3523
03:05:03,200 --> 03:05:04,680
IN THESE PATIENCE ONE BLOATING 

3524
03:05:04,680 --> 03:05:12,760
AFTER EATING COMMON IN IBS AND 

3525
03:05:12,760 --> 03:05:17,520
PAIN IN BOWEL MOVEMENT WHICH IS 

3526
03:05:17,520 --> 03:05:33,960
COMMON FROM CONSTANT TAKES IBS. 

3527
03:05:33,960 --> 03:05:40,720
>> WHETHER BACTERIA WHICH CAN 

3528
03:05:40,720 --> 03:05:42,960
CONVERT TRIP TOE FAN TO 

3529
03:05:42,960 --> 03:05:46,440
ACTIVATES A HOST RESENATOR WHICH

3530
03:05:46,440 --> 03:06:10,720
IS PRESENT ON THE EPITHELIUM. 

3531
03:06:10,720 --> 03:06:12,680
NEXT QUESTION IS WHERE IS THIS 

3532
03:06:12,680 --> 03:06:15,560
COMING FROM BECAUSE ESTABLISH 

3533
03:06:15,560 --> 03:06:21,120
THAT DIET IS THE SAME BUT IT CAN

3534
03:06:21,120 --> 03:06:26,840
CHANGE BASED ON THE MICROBES ARE

3535
03:06:26,840 --> 03:06:27,320
PRESENT. 

3536
03:06:27,320 --> 03:06:29,960
IT'S LIKE AN INCREASE IN 

3537
03:06:29,960 --> 03:06:31,360
MICROREPRODUCTION OF TRIP TOE 

3538
03:06:31,360 --> 03:06:34,280
FAN AND TRIP MEAN WHICH CAN BE 

3539
03:06:34,280 --> 03:06:35,920
DRIVEN BY THOSE MECHANISMS. 

3540
03:06:35,920 --> 03:06:38,400
THE IDEA OF DOING THIS KIND OF 

3541
03:06:38,400 --> 03:06:40,520
STUDY WAS TO IDENTIFY OR GET 

3542
03:06:40,520 --> 03:06:41,680
KNOWLEDGE AND THAT'S WHAT WE 

3543
03:06:41,680 --> 03:06:41,960
DID. 

3544
03:06:41,960 --> 03:06:46,040
SO WE LOOKED AT UNTARGETED ME 

3545
03:06:46,040 --> 03:06:52,880
TABLOIDS TO SEE IF THERE WOULD 

3546
03:06:52,880 --> 03:06:57,760
SEE -- AS YOU CAN SEE IT WAS 

3547
03:06:57,760 --> 03:07:00,480
FAIRLY CONSISTENT ACROSS SIX 

3548
03:07:00,480 --> 03:07:00,960
MONTHS. 

3549
03:07:00,960 --> 03:07:05,480
AGAIN, THE PROTEIN INTAKE . . . 

3550
03:07:05,480 --> 03:07:09,240
WAS SIMILAR AMONG THE TWO 

3551
03:07:09,240 --> 03:07:25,840
GROUPS. 

3552
03:07:25,840 --> 03:07:34,640
TOGETHER THIS CHANGED 

3553
03:07:34,640 --> 03:07:34,960
CORRELATED. 

3554
03:07:34,960 --> 03:07:44,360
SO IT'S A HOST . . .  WHICH IN 

3555
03:07:44,360 --> 03:07:48,680
FACT IS NOT CHANGED IN OUR 

3556
03:07:48,680 --> 03:07:49,360
COHORT OF CHANGES. 

3557
03:07:49,360 --> 03:07:51,160
WE WENT BACK TO THE DRAWING 

3558
03:07:51,160 --> 03:07:55,520
BOARD AND SAID THERE'S INCREASED

3559
03:07:55,520 --> 03:07:57,120
PRODUCTION OF . . .  IN 

3560
03:07:57,120 --> 03:07:59,840
CONSTIPATION PATIENTS AN 

3561
03:07:59,840 --> 03:08:02,800
IDENTIFIED USING A SIMILAR 

3562
03:08:02,800 --> 03:08:06,080
METHODOLOGY WHICH CORRELATES 

3563
03:08:06,080 --> 03:08:13,360
CONSUMPTION OF HYPO ZAN TEEN. 

3564
03:08:13,360 --> 03:08:16,040
WHEN WE DID THIS EXPERIMENT 

3565
03:08:16,040 --> 03:08:20,080
LOOKING AT BOTH PRODUCERS AN 

3566
03:08:20,080 --> 03:08:21,960
CONSUMERS YOU SEE INCREASED IN 

3567
03:08:21,960 --> 03:08:25,040
THE PRODUCERS LOW LEVEL IN 

3568
03:08:25,040 --> 03:08:26,520
CONSUMERS BUT WHAT SURPRISED US 

3569
03:08:26,520 --> 03:08:28,200
MEASURE GUT TRANSIT TIME IT WAS 

3570
03:08:28,200 --> 03:08:33,480
MUCH LONGER IN THE MICE WHICH 

3571
03:08:33,480 --> 03:08:35,120
SUGGESTED WE HAVE A ROLE TO PLAY

3572
03:08:35,120 --> 03:08:52,640
IN G. I. TRANSIT. 

3573
03:08:52,640 --> 03:08:54,760
>> YOU HAVE ABOUT TWO MINUTES. 

3574
03:08:54,760 --> 03:08:59,120
>> MECHANISM CAN WHICH AFFECT 

3575
03:08:59,120 --> 03:09:06,800
HYPER ZAN TEEN BU TRAIT LEVELS, 

3576
03:09:06,800 --> 03:09:08,360
SO DEPENDING ON MECHANISMS IF 

3577
03:09:08,360 --> 03:09:10,640
YOU THINK OF IT WE WENT FROM 

3578
03:09:10,640 --> 03:09:13,760
MECHANISMS IN EACH INDIVIDUAL. 

3579
03:09:13,760 --> 03:09:19,760
HOW DO WE CLASSIFY THEM, IF YOU 

3580
03:09:19,760 --> 03:09:23,760
LOOK AT THE SUMMARY THE POINT I 

3581
03:09:23,760 --> 03:09:26,680
WANTED TO MAKE THERE'S A CHANGE 

3582
03:09:26,680 --> 03:09:30,160
IN BACTERIA METABOLITES CAN 

3583
03:09:30,160 --> 03:09:34,160
CHANGE IN G. I. FUNCTION. 

3584
03:09:34,160 --> 03:09:38,520
CONTEXT MATTERS BECAUSE WHICH I 

3585
03:09:38,520 --> 03:09:41,560
SHOWED EXAMPLES OF FUNCTION IN 

3586
03:09:41,560 --> 03:09:45,520
THE BIODISEASE BUT IT COULD

3587
03:09:45,520 --> 03:09:50,520
COULD . . .  IBS SPAISHTS. 

3588
03:09:50,520 --> 03:09:54,680
INDIVIDUAL METABOLITES MY SINNER

3589
03:09:54,680 --> 03:10:02,800
JIES OR METABOLIZE EACH OTHER. 

3590
03:10:02,800 --> 03:10:08,560
THESE KIND OF LONGITUDAL STUDIES

3591
03:10:08,560 --> 03:10:10,920
CAN IDENTIFY MECHANISMS. 

3592
03:10:10,920 --> 03:10:14,360
NOT ALL DISEASE IS DRIVEN BY 

3593
03:10:14,360 --> 03:10:18,680
MICROBIOME AND MIKE OH THERAPIES

3594
03:10:18,680 --> 03:10:21,000
WILL NOT CURE THEM ALL. 

3595
03:10:21,000 --> 03:10:22,800
LOOKING AT PROBIOTICS WE ARE 

3596
03:10:22,800 --> 03:10:24,080
LOOKING IN THREE DIFFERENT 

3597
03:10:24,080 --> 03:10:25,960
REGIONS AN THAT'S WHAT YOU ARE 

3598
03:10:25,960 --> 03:10:28,280
GOING TO HEAR THROUGHOUT THIS 

3599
03:10:28,280 --> 03:10:28,960
CONFERENCE. 

3600
03:10:28,960 --> 03:10:33,360
I MENTIONED MICROBIOTIC 

3601
03:10:33,360 --> 03:10:35,200
THERAPIES ARE IMPORTANT F. THIS 

3602
03:10:35,200 --> 03:10:41,160
MECHANISM IS CRITICAL FOR THE 

3603
03:10:41,160 --> 03:10:45,040
PHENOTYPE AND HOW TO FIND A 

3604
03:10:45,040 --> 03:10:48,360
PROBIOTIC AND THERAPY AND HOW TO

3605
03:10:48,360 --> 03:10:51,000
DEFINE CLINICAL TRIALS OR 

3606
03:10:51,000 --> 03:10:54,400
RETHINK CLINICAL TRIALS TO 

3607
03:10:54,400 --> 03:10:56,680
TARG

3608
03:10:56,680 --> 03:10:56,920
TARGET. 

3609
03:10:56,920 --> 03:10:58,360
ALL THIS WORK IS DONE WITH 

3610
03:10:58,360 --> 03:11:01,960
STUDENTS IN MY LAB AND 

3611
03:11:01,960 --> 03:11:05,760
COLLABORATOR LABS AND IBS STUDY 

3612
03:11:05,760 --> 03:11:09,720
STORTD BY NIH IN COLLABORATION 

3613
03:11:09,720 --> 03:11:11,120
WITH UNIVERSITY OF MINNESOTA AN 

3614
03:11:11,120 --> 03:11:12,320
LOOK FORWARD TO GOOD DISCUSSION 

3615
03:11:12,320 --> 03:11:14,440
ON THAT. 

3616
03:11:14,440 --> 03:11:16,080
THANK YOU. 

3617
03:11:16,080 --> 03:11:18,640
>> DR. KASHYAP THANKS FOR 

3618
03:11:18,640 --> 03:11:20,480
SETTING LIGHT ON A DISEASE THAT 

3619
03:11:20,480 --> 03:11:22,640
HAS BEEN SORT OF THOUGHT OF AS 

3620
03:11:22,640 --> 03:11:25,600
PSYCHOLOGICAL ILLNESS. 

3621
03:11:25,600 --> 03:11:28,840
YOU BROUGHT SOME VERY IMPORTANT 

3622
03:11:28,840 --> 03:11:32,560
INFORMATION ABOUT THE PATHOGEN 

3623
03:11:32,560 --> 03:11:34,320
ASSIST. 

3624
03:11:34,320 --> 03:11:39,520
NEXT SPEAKER IS DR. DR. HAMMER 

3625
03:11:39,520 --> 03:11:42,920
IN RESPONSE TO REGULATION 

3626
03:11:42,920 --> 03:11:46,400
METABOLIC REWIRING LONG FETAL 

3627
03:11:46,400 --> 03:11:49,720
DERIVED FETAL CELLS MANY 

3628
03:11:49,720 --> 03:11:55,760
DR. HAMMER. 

3629
03:11:55,760 --> 03:12:00,200
>> DR. HAMMER, YOU NEED TO 

3630
03:12:00,200 --> 03:12:09,880
UNMUTE, PLEASE. 

3631
03:12:09,880 --> 03:12:12,600
>> MY NAME IS GIANNA HAMMER. 

3632
03:12:12,600 --> 03:12:14,520
I'M IN THE PROCESS OF MOVING TO 

3633
03:12:14,520 --> 03:12:15,520
UNIVERSITY OF UTAH AT SALT LAKE 

3634
03:12:15,520 --> 03:12:19,240
CITY THIS COMING JUNE. 

3635
03:12:19,240 --> 03:12:29,600
SO, FOCUS WILL BE ON LONG LIVED 

3636
03:12:29,600 --> 03:12:31,520
FEE AT ALL DERIVED CELLS AND 

3637
03:12:31,520 --> 03:12:34,160
THEIR ZEAL FOR THE MICROBIOME 

3638
03:12:34,160 --> 03:12:36,000
AND A QUESTION I'VE BEEN 

3639
03:12:36,000 --> 03:12:38,520
THINKING IS WHAT HOST 

3640
03:12:38,520 --> 03:12:39,680
MICRODYNAMICS ARE OPEN FOR 

3641
03:12:39,680 --> 03:12:40,960
LEARNING N. MY LAB WE NEVER TAKE

3642
03:12:40,960 --> 03:12:42,560
FOR GRANTED THE RULES ARE GOING 

3643
03:12:42,560 --> 03:12:46,520
TO BE THE SAME IN ALL CONTEXT 

3644
03:12:46,520 --> 03:12:51,000
DEPENDING ON SMALL INTESTINE OR 

3645
03:12:51,000 --> 03:12:53,240
COLON, TUMORS vs. NORMAL TISSUE 

3646
03:12:53,240 --> 03:12:57,360
SO WE DON'T TAKE IT FOR GRANTED 

3647
03:12:57,360 --> 03:13:00,720
THAT EVERYTHING WILL ACCULTURE 

3648
03:13:00,720 --> 03:13:03,280
ALWAYS SO WE ARE LOOKING FOR 

3649
03:13:03,280 --> 03:13:03,960
THINGS FLEXIBLE. 

3650
03:13:03,960 --> 03:13:07,760
SO OUR FOCUS WILL BE ON GAMMA 

3651
03:13:07,760 --> 03:13:11,400
DELTA T CELLS AND I NEVER EVEN 

3652
03:13:11,400 --> 03:13:15,400
SAID THE WORDS DELTA GAMMA T 

3653
03:13:15,400 --> 03:13:17,640
CELL UNTIL MY STUDENTS SHOW HOW 

3654
03:13:17,640 --> 03:13:20,320
LONG THEY EXPAND IN COLON 

3655
03:13:20,320 --> 03:13:20,560
TUMORS.  

3656
03:13:20,560 --> 03:13:22,480
THEY'VE CONSUMED A LOT OF MY 

3657
03:13:22,480 --> 03:13:27,040
THOUGHT NOW BECAUSE I REALIZE 

3658
03:13:27,040 --> 03:13:28,960
AFTER MY STUDENT POINTED OUT 

3659
03:13:28,960 --> 03:13:31,880
THERE'S A BIG GAP ABOUT HOW 

3660
03:13:31,880 --> 03:13:36,160
THESE REACT WITH MICROBIOTA SO 

3661
03:13:36,160 --> 03:13:42,200
GAMMA DELTA T CELLS COME IN TWO 

3662
03:13:42,200 --> 03:13:43,360
TYPES. 

3663
03:13:43,360 --> 03:13:44,800
BOTH THOSE MICROBES ARE 

3664
03:13:44,800 --> 03:13:46,600
DIFFERENT FROM CONVENTIONAL T 

3665
03:13:46,600 --> 03:13:48,880
CELLS SO THEY CAN SENSE MICROBES

3666
03:13:48,880 --> 03:13:55,000
EVEN DIRECTLY AND INDIRECTLY SO 

3667
03:13:55,000 --> 03:13:59,720
ANOTHER CELL WILL SEE A SIGNAL 

3668
03:13:59,720 --> 03:14:01,760
SIGHT KIND AND TURN ON 

3669
03:14:01,760 --> 03:14:02,160
FUNCTIONS. 

3670
03:14:02,160 --> 03:14:06,840
THE DELTA GAMMA ARE DEFINITELY T

3671
03:14:06,840 --> 03:14:07,080
CELLS.  

3672
03:14:07,080 --> 03:14:12,720
THEY HAVE A T CELL RESENATOR BUT

3673
03:14:12,720 --> 03:14:14,920
IT'S DEBATABLE WHETHER THEY NEED

3674
03:14:14,920 --> 03:14:17,400
THE T CELL TO DO THEIR FUNCTION.

3675
03:14:17,400 --> 03:14:18,960
THE INTEREST TO ME HAS BEEN THE 

3676
03:14:18,960 --> 03:14:21,960
FLAVOR THAT MAKES IL-17.  

3677
03:14:21,960 --> 03:14:24,160
THE REASON IS THIS CLASS IS 

3678
03:14:24,160 --> 03:14:27,120
GAMMA DELTA T CELLS IS ALMOST 

3679
03:14:27,120 --> 03:14:30,400
CONCLUSIVELY MADE DURING FETAL 

3680
03:14:30,400 --> 03:14:30,920
LIFE. 

3681
03:14:30,920 --> 03:14:34,080
SO, DURING FETAL LIFE IT 

3682
03:14:34,080 --> 03:14:36,560
DEVELOPS THESE CELLS AND THESE 

3683
03:14:36,560 --> 03:14:40,960
ARE ENTERING THE BARRIER TISSUES

3684
03:14:40,960 --> 03:14:43,960
SO SINCE THERE'S A STRONG 

3685
03:14:43,960 --> 03:14:45,240
PREFERENCE, DUST DON'T MAKE 

3686
03:14:45,240 --> 03:14:48,840
THESE TYPES OF T CELLS. 

3687
03:14:48,840 --> 03:14:52,200
THIS MEANS THESE CELLS ARE 

3688
03:14:52,200 --> 03:14:53,800
SENSITIVE TO RADIATION AND NOT 

3689
03:14:53,800 --> 03:14:56,200
HAVE OPPORTUNITIES TO COME BACK.

3690
03:14:56,200 --> 03:14:59,600
IF THERE'S PADS GENERAL INDUCED 

3691
03:14:59,600 --> 03:15:01,720
OR REASON WHY THEY DIE AGAIN 

3692
03:15:01,720 --> 03:15:03,560
THEY WILL NOT HAVE OPPORTUNITY 

3693
03:15:03,560 --> 03:15:04,520
TO COME BACK. 

3694
03:15:04,520 --> 03:15:07,560
THESE ARE FETAL DERIVED AND THEY

3695
03:15:07,560 --> 03:15:09,360
STAY IN THE BODY THROUGHOUT THE 

3696
03:15:09,360 --> 03:15:09,640
LIFETIME. 

3697
03:15:09,640 --> 03:15:13,120
THEY'RE PRIMARILY RESIDENT IN 

3698
03:15:13,120 --> 03:15:16,840
BARRIER TISSUES WHERE MICROBIOTA

3699
03:15:16,840 --> 03:15:19,520
ARE DOMINANT. 

3700
03:15:19,520 --> 03:15:21,240
IN THESE BARRIER TISSUES THEY 

3701
03:15:21,240 --> 03:15:22,760
ARE IMPORTANT FOR PATHOGEN 

3702
03:15:22,760 --> 03:15:23,000
DEFENSE. 

3703
03:15:23,000 --> 03:15:26,400
IN SOME CASES THEY DEFINITELY 

3704
03:15:26,400 --> 03:15:28,880
HAVE ROLES OR MISBEHAVIORS IN 

3705
03:15:28,880 --> 03:15:31,440
DISEASE BUT THEY ALSO HAVE HAD 

3706
03:15:31,440 --> 03:15:37,960
IMPORTANT TISSUE HOMEIO STAYSIES

3707
03:15:37,960 --> 03:15:39,520
AND SO FORTH. 

3708
03:15:39,520 --> 03:15:41,520
THEY ALSO LIVE IN OTHER TISSUES 

3709
03:15:41,520 --> 03:15:44,400
AND ONE THING I WON'T TOUCH UPON

3710
03:15:44,400 --> 03:15:48,760
IS THEY ALSO RESIDE IN THE MEAN 

3711
03:15:48,760 --> 03:15:53,200
JEEZ OF THE BRAIN. 

3712
03:15:53,200 --> 03:15:56,320
2019 HAVE BEEN INDICATED IN 

3713
03:15:56,320 --> 03:15:59,560
SHORT TERM MEMORY ANXIETY AND 

3714
03:15:59,560 --> 03:16:00,320
SOCIALABILITY. 

3715
03:16:00,320 --> 03:16:01,920
SO FROM THESE DIFFERENT CONTEXT 

3716
03:16:01,920 --> 03:16:04,360
BEING IN THE BRAIN, THEY CAN 

3717
03:16:04,360 --> 03:16:08,200
INTERACT WITH MICROBIOTA OUR 

3718
03:16:08,200 --> 03:16:09,560
QUESTION HAS BEEN HOW DO THESE 

3719
03:16:09,560 --> 03:16:16,160
LONG LIVED FETAL DERIVED CELLS 

3720
03:16:16,160 --> 03:16:20,440
INTERACT WITH PROBIOTICS AND HOW

3721
03:16:20,440 --> 03:16:26,440
THEY INTERACT WITH MIKE. 

3722
03:16:26,440 --> 03:16:27,960
MAYBE THEY'RE CONTINUOUS 

3723
03:16:27,960 --> 03:16:28,320
LEARNINGERS. 

3724
03:16:28,320 --> 03:16:30,600
MAYBE THEY CONSTANTLY INTERACT 

3725
03:16:30,600 --> 03:16:32,760
WITH MICROBES KEEPING WITH BEING

3726
03:16:32,760 --> 03:16:34,640
FLEXIBLE WHAT THEY DO AND BEHAVE

3727
03:16:34,640 --> 03:16:36,360
AND THEY COULD BE QUITE FIXED. 

3728
03:16:36,360 --> 03:16:38,880
MAY THEY COME OUT OF THE FETAL 

3729
03:16:38,880 --> 03:16:41,960
THYMUS AND ONCE THE BABY IS 

3730
03:16:41,960 --> 03:16:44,200
COLONIZED WITH FULL SET OF 

3731
03:16:44,200 --> 03:16:47,360
MICROBIOTA MAYBE YOU'RE ONE AND 

3732
03:16:47,360 --> 03:16:50,200
DONE SO WE BASICALLY WE WANTED 

3733
03:16:50,200 --> 03:16:54,360
TO MAKE HEAD WAY ON THESE QUITE 

3734
03:16:54,360 --> 03:16:57,080
SIMPLE QUESTIONS. 

3735
03:16:57,080 --> 03:16:58,280
WE HAVE TO ASK WHAT DOES 

3736
03:16:58,280 --> 03:16:59,760
LEARNING LOOK LIKE, WHAT THE 

3737
03:16:59,760 --> 03:17:00,920
KIND OF BEHAVIORS MIGHT BE 

3738
03:17:00,920 --> 03:17:03,160
REGULATED BY THE MICROBIOME. 

3739
03:17:03,160 --> 03:17:06,720
THE SCIENTIFIC SENSE WHAT DO WE 

3740
03:17:06,720 --> 03:17:08,280
AS SAY. 

3741
03:17:08,280 --> 03:17:10,840
SO FROM STUDNESS GERM FREE MICE 

3742
03:17:10,840 --> 03:17:12,720
WE KNEW THAT CELL NUMBER AND 

3743
03:17:12,720 --> 03:17:14,760
EVEN THE FORM OF PRODUCTION BY 

3744
03:17:14,760 --> 03:17:17,280
THESE DEDICATED CELLS IS 

3745
03:17:17,280 --> 03:17:19,280
ACTUALLY NOT SOMETHING VERY EASY

3746
03:17:19,280 --> 03:17:21,080
TO SEE IS GOING TO BE LINKED TO 

3747
03:17:21,080 --> 03:17:23,040
THE MICROBIOTA. 

3748
03:17:23,040 --> 03:17:26,200
SO IN ASKING ABOUT HOW WHAT WE 

3749
03:17:26,200 --> 03:17:27,520
ACTUALLY LOOK FOR AND HOW THESE 

3750
03:17:27,520 --> 03:17:31,360
ARE RESPONDING TO THE MICROBES 

3751
03:17:31,360 --> 03:17:33,640
WE AGAIN REALIZE COMPARATIVE 

3752
03:17:33,640 --> 03:17:38,960
ANALYSIS OF THE TWO FLAVORS, 

3753
03:17:38,960 --> 03:17:41,160
THEY BOTH LIVE IN THE GUT AND WE

3754
03:17:41,160 --> 03:17:44,320
OF COURSE IF THIS WAS, IF WE HAD

3755
03:17:44,320 --> 03:17:48,360
LEVERAGE TO DO ANY KIND OF 

3756
03:17:48,360 --> 03:17:52,960
TRANCE RICK TOMICS HAD A THAT IS

3757
03:17:52,960 --> 03:17:55,160
NOT BEEN INFORMS FOR THESE IN 

3758
03:17:55,160 --> 03:17:57,720
THE GUT WITH THE TOOLS AND 

3759
03:17:57,720 --> 03:18:01,160
KNOWLEDGE THAT WE CAN MAKE HEAD 

3760
03:18:01,160 --> 03:18:08,400
WAY ON THAT. 

3761
03:18:08,400 --> 03:18:10,360
PEOPLE TELL THE DIFFERENCE 

3762
03:18:10,360 --> 03:18:12,760
BETWEEN THESE T CELLS THAT DON'T

3763
03:18:12,760 --> 03:18:14,160
WORK IN THE GUT HENCE WHY 

3764
03:18:14,160 --> 03:18:17,520
THERE'S A GAP IN THE FIELD HOW 

3765
03:18:17,520 --> 03:18:19,680
THEY'RE BEHAVING IN THE SATTIN. 

3766
03:18:19,680 --> 03:18:21,880
SO TO ASK HOW THESE CELLS ARE 

3767
03:18:21,880 --> 03:18:24,960
DIFFERENT AND INTERACTING WITH 

3768
03:18:24,960 --> 03:18:27,520
MICROBIOTA WE DID A SAMPLE . . .

3769
03:18:27,520 --> 03:18:29,520
READING OF MARKERS ASSOCIATED 

3770
03:18:29,520 --> 03:18:29,920
WITH ACTIVATION. 

3771
03:18:29,920 --> 03:18:33,400
SO IF THE CELL IS GOING TO BE

3772
03:18:33,400 --> 03:18:37,440
BE . . .  BY A MICROBE WE HAVE 

3773
03:18:37,440 --> 03:18:47,960
MOLECULES THAT MIGHT BE CHANGING

3774
03:18:47,960 --> 03:18:48,200
CHANGING. 

3775
03:18:48,200 --> 03:18:50,880
WE DIDN'T FIND A GREAT SET OF 

3776
03:18:50,880 --> 03:18:51,160
MARKERS. 

3777
03:18:51,160 --> 03:18:54,200
A GREAT SET THAT TOLD US THERE 

3778
03:18:54,200 --> 03:18:56,720
WERE REMARK DIFFICULTIESES FOR 

3779
03:18:56,720 --> 03:18:59,720
EVERYTHING WITH THE EXCEPTION OF

3780
03:18:59,720 --> 03:19:03,760
ONE MOLECULE. 

3781
03:19:03,760 --> 03:19:05,880
THIS MOLECULE WAS HIGHLY 

3782
03:19:05,880 --> 03:19:08,600
DISTINCT IN EXPRESSION. 

3783
03:19:08,600 --> 03:19:13,880
WE PARTNER'S THIS TD-1 

3784
03:19:13,880 --> 03:19:15,160
EXPRESSION WITH ANOTHER MODEL 

3785
03:19:15,160 --> 03:19:19,760
THAT HAD BASICALLY A MESSY HIS 

3786
03:19:19,760 --> 03:19:21,960
TOE GRAM BUT PUT THESE TWO 

3787
03:19:21,960 --> 03:19:23,600
TOGETHER IT NICELY SEPARATED A 

3788
03:19:23,600 --> 03:19:25,000
POPULATION THAT WAS PURRAGEOUS 

3789
03:19:25,000 --> 03:19:29,160
DYNA D-1 POSITIVE AND POPULATION

3790
03:19:29,160 --> 03:19:30,040
PD-1 NEGATIVE AND ANOTHER 

3791
03:19:30,040 --> 03:19:31,520
POPULATION THAT WAS A BUMP IN 

3792
03:19:31,520 --> 03:19:36,720
THE ELBOW IF YOU WILL OF GAMMA 

3793
03:19:36,720 --> 03:19:37,760
DELTA T CELLS. 

3794
03:19:37,760 --> 03:19:46,120
IF WE FOCUS ON THE PD-1 THEY DID

3795
03:19:46,120 --> 03:19:47,520
NOT MAKE THE SIEPT KIND 

3796
03:19:47,520 --> 03:19:48,840
INTERFERING GAMMA. 

3797
03:19:48,840 --> 03:19:51,600
FOCUSSING ON THE NEGATIVE 

3798
03:19:51,600 --> 03:19:54,640
POPULATION WILL MAKE THE SIGHT 

3799
03:19:54,640 --> 03:19:58,120
KIND INTER FERN GAMMA DND MAINL 

3800
03:19:58,120 --> 03:20:00,160
AISLE 17 AND THE MINOR BUMP IF 

3801
03:20:00,160 --> 03:20:02,440
WE SIMULATE THOSE THEY WERE A 

3802
03:20:02,440 --> 03:20:05,080
MIX OF BOTH TYPES OF GAMMA DELTA

3803
03:20:05,080 --> 03:20:07,440
T CELL AND WE BROUGHT THIS UP AS

3804
03:20:07,440 --> 03:20:09,160
WELL WITH GENE EXPRESSION 

3805
03:20:09,160 --> 03:20:12,600
ANALYSIS SO LOOKING AT 

3806
03:20:12,600 --> 03:20:15,800
POPULATION 1 THESE HAVE AISLE 17

3807
03:20:15,800 --> 03:20:19,360
A AND AISLE 17 F. 

3808
03:20:19,360 --> 03:20:22,520
POPULATION 2 DOES HAVE 

3809
03:20:22,520 --> 03:20:23,600
INTERFERON GAMMA. 

3810
03:20:23,600 --> 03:20:26,160
SO ALSO WE DID THE ANALYSIS WITH

3811
03:20:26,160 --> 03:20:28,680
THE MASTER TRANSCRIPTION FACTOR 

3812
03:20:28,680 --> 03:20:32,160
THAT IT ALLOWS CELLS TO MAKE 

3813
03:20:32,160 --> 03:20:34,480
AISLE 17. 

3814
03:20:34,480 --> 03:20:37,600
ALL THESE CELLS WERE POSITIVE 

3815
03:20:37,600 --> 03:20:38,960
AND NEGATIVE AND LITTLE BUMP ON 

3816
03:20:38,960 --> 03:20:43,520
OUR ELBOW WAS A MIX OF BOTH 

3817
03:20:43,520 --> 03:20:47,000
POPULATIONS BUT IT WAS CLEAR 

3818
03:20:47,000 --> 03:20:49,440
THEY'RE OF THE AISLE 17 FLAVOR 

3819
03:20:49,440 --> 03:20:50,480
OR POPULATION. 

3820
03:20:50,480 --> 03:20:53,040
SO WITH THIS SET OF RULES WHERE 

3821
03:20:53,040 --> 03:20:56,320
WE KNEW PD-1 WE KNEW THAT THESE 

3822
03:20:56,320 --> 03:20:59,200
WERE THE GAMMA DELTA 17'S AND 

3823
03:20:59,200 --> 03:21:01,800
THE PD-1 NEGATIVES WERE THE 

3824
03:21:01,800 --> 03:21:05,360
INTERFERON GAMMA PRODUCING 

3825
03:21:05,360 --> 03:21:05,680
POPULATION. 

3826
03:21:05,680 --> 03:21:08,360
WE COULD ATTENUATE WHAT THE 

3827
03:21:08,360 --> 03:21:10,840
MICROBIOTA WERE DOING TO CHANGE 

3828
03:21:10,840 --> 03:21:11,080
THESE. 

3829
03:21:11,080 --> 03:21:13,040
SO WE COULD HAVE A CELEBRATION 

3830
03:21:13,040 --> 03:21:15,120
SAYING IT'S IMPOSSIBLE FOR US TO

3831
03:21:15,120 --> 03:21:16,240
TELL THE DIFFERENCE WITH THESE 

3832
03:21:16,240 --> 03:21:19,680
CELLS IN THE GUPT AND FIGURE OUT

3833
03:21:19,680 --> 03:21:22,160
WHAT THEY'RE DOING BUT THAT 

3834
03:21:22,160 --> 03:21:25,480
WASN'T NECESSARILY THE PURPOSE 

3835
03:21:25,480 --> 03:21:25,680
HERE. 

3836
03:21:25,680 --> 03:21:28,120
OUR PURPOSE THEN ASKING AFTER WE

3837
03:21:28,120 --> 03:21:31,840
FOUND OUT PD-1 WAS A SUBSET OF 

3838
03:21:31,840 --> 03:21:34,160
POPULATIONS WHY ASKED WHY PD-1, 

3839
03:21:34,160 --> 03:21:35,960
IS MICROBIOTA AT FAULT AND WHAT 

3840
03:21:35,960 --> 03:21:39,160
IS THE FUNCTION OF PD-1 AND WHAT

3841
03:21:39,160 --> 03:21:41,560
IS THE ROLE IF ANY ON HUMAN 

3842
03:21:41,560 --> 03:21:42,080
HEALTH. 

3843
03:21:42,080 --> 03:21:46,360
SO TO TEST THE INFLUENCE OF 

3844
03:21:46,360 --> 03:21:50,760
MICROBIOTA WE DID THE ELBOW WITH

3845
03:21:50,760 --> 03:21:54,160
PEED B PEDIATRIC EXPRESSION AND 

3846
03:21:54,160 --> 03:21:57,960
WE GIVE THE ANTIBIOTICS TO ADULT

3847
03:21:57,960 --> 03:22:02,800
MICE OVER FOUR WEEKS AND THIS 

3848
03:22:02,800 --> 03:22:05,720
PD-1B EXPRESSION COLLAPSED 

3849
03:22:05,720 --> 03:22:07,800
LOOKING MORE LIKE A SOCK THAN A 

3850
03:22:07,800 --> 03:22:11,760
BOOT AND NOT BECAUSE THE FETAL 

3851
03:22:11,760 --> 03:22:17,560
DERIVED CELLS ARE DYING. 

3852
03:22:17,560 --> 03:22:19,640
HERE ARE THE POSITIVE FIELD 

3853
03:22:19,640 --> 03:22:21,400
DERIVED CELLS AN ANTIBIOTIC 

3854
03:22:21,400 --> 03:22:21,720
TREATMENT. 

3855
03:22:21,720 --> 03:22:26,000
THE PD 1 IS BACKWARD BUT WE HAVE

3856
03:22:26,000 --> 03:22:28,760
THAT GAMMA T POPULATION. 

3857
03:22:28,760 --> 03:22:30,960
THEY JUST DON'T HAVE PD-1 

3858
03:22:30,960 --> 03:22:33,720
ANYMORE SO WE KNOW THE PD-1 

3859
03:22:33,720 --> 03:22:35,120
EXPRESSION IS NOT A PERMANENT 

3860
03:22:35,120 --> 03:22:36,640
MARKER ON THIS POPULATION. 

3861
03:22:36,640 --> 03:22:38,960
WE ALSO DON'T NEED TO IT LIVE OR

3862
03:22:38,960 --> 03:22:42,480
EXIST OR ANYTHING BUT 

3863
03:22:42,480 --> 03:22:47,760
IMPORTANTLY, PD-1 IS SUSTAINED. 

3864
03:22:47,760 --> 03:22:49,960
IT'S GREAT EVIDENCE TO SAY THESE

3865
03:22:49,960 --> 03:22:52,760
CELLS ARE CONSTANTLY RECEIVING 

3866
03:22:52,760 --> 03:22:55,400
STIMULUS FROM THOSE MICROBES. 

3867
03:22:55,400 --> 03:22:57,560
SO OUR ONLY PATH TO LOOK AT THE 

3868
03:22:57,560 --> 03:23:01,960
MICROBES THAT HAVE A DOMINANT 

3869
03:23:01,960 --> 03:23:06,840
INFLUENCE IN THIS HERE IS A HIS 

3870
03:23:06,840 --> 03:23:16,760
TOE GRAM EVERYTHING ELSE TESTED 

3871
03:23:16,760 --> 03:23:51,240
DID HAVE SOME EFFECT. 

3872
03:23:51,240 --> 03:23:56,080
THIS COMES DOWN TO ASKING DOES 

3873
03:23:56,080 --> 03:23:57,320
PD-1 HAVE A FUNCTION. 

3874
03:23:57,320 --> 03:23:59,920
AS CONTINUOUSLY EXPRESSED HAVE A

3875
03:23:59,920 --> 03:24:00,520
FUNCTION. 

3876
03:24:00,520 --> 03:24:05,160
SO AS YOU MAY KNOW PD 1 IS 

3877
03:24:05,160 --> 03:24:14,720
FAMOUS AS A T CELL INHIBITOR

3878
03:24:14,720 --> 03:24:17,360
INHIBITOR . . .  FOR THEIR 

3879
03:24:17,360 --> 03:24:56,960
DISCOVER BEFORE SO IS MICROBIOTA

3880
03:24:56,960 --> 03:25:00,760
INHIBITOR AND IF SO THIS COMES 

3881
03:25:00,760 --> 03:25:04,760
DOWN TO WHAT DO WE AS SAY. 

3882
03:25:04,760 --> 03:25:08,600
THERE'S CONFLICTING DATA ON 

3883
03:25:08,600 --> 03:25:15,080
GAMMA DELTA T CELLS SO IN 2010 A

3884
03:25:15,080 --> 03:25:18,680
STUDY SUGGESTED IF YOU PUT 

3885
03:25:18,680 --> 03:25:40,320
MICROBIOTA ON SO WHAT DO WE ARE 

3886
03:25:40,320 --> 03:25:44,360
WE GOING TO ASSAY. 

3887
03:25:44,360 --> 03:25:51,040
WE FOCUS ON AISLE 17 GFP 

3888
03:25:51,040 --> 03:25:54,160
REPORTER. 

3889
03:25:54,160 --> 03:25:56,960
SO, CERTAINLY THE PD-1 POSITIVES

3890
03:25:56,960 --> 03:26:01,880
ARE MAKING AISLE 17. 

3891
03:26:01,880 --> 03:26:04,520
THIS IS THE CONTROL, THE DATA IS

3892
03:26:04,520 --> 03:26:06,760
BLACK AND WHITE THAT MICROBIOTA 

3893
03:26:06,760 --> 03:26:10,280
ARE A NATURAL AISLE 17 

3894
03:26:10,280 --> 03:26:16,680
PRODUCTION. 

3895
03:26:16,680 --> 03:26:19,040
BUT ANOTHER THING I'LL JUST 

3896
03:26:19,040 --> 03:26:22,560
QUICKLY TOUCH BEYOND, WE ALSO 

3897
03:26:22,560 --> 03:26:34,040
FOUND SIMILARITIES IN GENITAL 

3898
03:26:34,040 --> 03:26:36,200
TRACK AS WELL AS THE LUNGS. 

3899
03:26:36,200 --> 03:26:39,360
MICROBIOTA ARE FOR IMPORTANT 

3900
03:26:39,360 --> 03:26:44,600
MAKING THAT. 

3901
03:26:44,600 --> 03:26:47,040
SO, NOW WE KNOW THAT MICROBIOTA 

3902
03:26:47,040 --> 03:26:48,720
ARE CONSTANTLY STIMULATING OUR 

3903
03:26:48,720 --> 03:26:50,160
GAMMA DELTAS. 

3904
03:26:50,160 --> 03:26:52,400
WE IDENTIFIED PD-1 AS SOMETHING 

3905
03:26:52,400 --> 03:26:53,720
THAT COMES OUT OF THIS 

3906
03:26:53,720 --> 03:26:54,960
RELATIONSHIP BUT IMPORTANTLY 

3907
03:26:54,960 --> 03:27:01,680
IT'S A BINARY THING. 

3908
03:27:01,680 --> 03:27:06,760
WE JUST GAVE PD-1 ANTIBODIES AND

3909
03:27:06,760 --> 03:27:09,520
SURE ENOUGH THERE'S AN INCREASE 

3910
03:27:09,520 --> 03:27:11,480
IN THE AMOUNT PRODUCED.

3911
03:27:11,480 --> 03:27:16,560
WE KNOW BOTH MOLECULES CAN BE 

3912
03:27:16,560 --> 03:27:18,080
DYNAMICLY REGULATED. 

3913
03:27:18,080 --> 03:27:20,040
SO, WE WANTED TO ASK ABOUT 

3914
03:27:20,040 --> 03:27:23,640
UNIQUE EXPRESSION MODALITIES IN 

3915
03:27:23,640 --> 03:27:27,560
SETTING UP MICROBIAL BIOSIS. 

3916
03:27:27,560 --> 03:27:30,360
IN THE CUTE MODEL WE ACTUALLY 

3917
03:27:30,360 --> 03:27:33,440
FOUND THAT YES, THE GAMMA DELTA 

3918
03:27:33,440 --> 03:27:36,400
TURN UP AISLE 17 BUT ALSO PD-1. 

3919
03:27:36,400 --> 03:27:40,080
AND FUNNY ENOUGH IF YOU LOOK AT 

3920
03:27:40,080 --> 03:27:45,480
THE RESOLUTION PHASE SOMEHOW 

3921
03:27:45,480 --> 03:27:49,040
THESE CHANGES ARE LONG LIVED 

3922
03:27:49,040 --> 03:27:52,040
BECAUSE WELL AFTER THE 

3923
03:27:52,040 --> 03:27:54,080
INFLAMMATION THEY HAVE AUGMENTED

3924
03:27:54,080 --> 03:27:54,360
RESPONSES. 

3925
03:27:54,360 --> 03:27:56,720
DATA I SHOW, THIS IS A SUMMARY 

3926
03:27:56,720 --> 03:27:58,560
ABOUT THE AUGMENTED BEHAVIOR 

3927
03:27:58,560 --> 03:28:01,200
HERE BUT WE ALSO FIND THAT AFTER

3928
03:28:01,200 --> 03:28:04,480
AN INSULT THESE GAMMA DELTA'S 

3929
03:28:04,480 --> 03:28:07,920
LEARN NEW BEHAVIORS WHERE THEY 

3930
03:28:07,920 --> 03:28:11,760
DECIDE TO LIVE. 

3931
03:28:11,760 --> 03:28:14,400
SO IN LOOKING FOR WHAT MIGHT BE 

3932
03:28:14,400 --> 03:28:17,320
BEHIND THIS KIND OF LEARNING 

3933
03:28:17,320 --> 03:28:19,160
EXPERIENCE, WE IDENTIFIED 

3934
03:28:19,160 --> 03:28:22,720
INCREASED LIPID UP TAKE THAT 

3935
03:28:22,720 --> 03:28:26,400
HAPPENED IN FECAL DERIVED IMMUNE

3936
03:28:26,400 --> 03:28:30,160
TELLS AND PUT TOGETHER DATA THAT

3937
03:28:30,160 --> 03:28:33,440
AISLE 17 AND PD 1 CAN GO AS WELL

3938
03:28:33,440 --> 03:28:41,480
AS INCREASED UP TAKE. 

3939
03:28:41,480 --> 03:28:45,160
SO I'LL WRAP IT UP. 

3940
03:28:45,160 --> 03:28:47,760
I JUST HAVE LISTED SOME 

3941
03:28:47,760 --> 03:28:51,000
QUESTIONS THAT WE CAN THINK 

3942
03:28:51,000 --> 03:28:55,960
ABOUT FOR OUR FUTURE DISCUSSION 

3943
03:28:55,960 --> 03:28:59,360
DYNAMIC INTERPLAY WITH THESE 

3944
03:28:59,360 --> 03:29:03,120
CELLS, WE ARE INTERESTED IN HOW 

3945
03:29:03,120 --> 03:29:04,360
THIS CONTRIBUTES TO CELLS 

3946
03:29:04,360 --> 03:29:07,800
INCLUDING THE GUT-BRAIN ACCESS 

3947
03:29:07,800 --> 03:29:10,800
AND HOW SPECIFICALLY MAY ALTER 

3948
03:29:10,800 --> 03:29:13,640
THE TIMELINE TO BASELINE. 

3949
03:29:13,640 --> 03:29:15,480
THAT IS ALL FOR MY TALK. 

3950
03:29:15,480 --> 03:29:16,400
THANK YOU SO MUCH. 

3951
03:29:16,400 --> 03:29:18,800
>> THANK YOU DR. HAMMER. 

3952
03:29:18,800 --> 03:29:21,440
THAT WAS AN OUTSTANDING TALK ON 

3953
03:29:21,440 --> 03:29:26,160
IMMUNE DYSFUNCTION AN PD-1 

3954
03:29:26,160 --> 03:29:26,800
EXPRESSION AND AISLE 17 

3955
03:29:26,800 --> 03:29:29,760
THOUGHTFUL PRESENTATION. 

3956
03:29:29,760 --> 03:29:34,160
THANK YOU AGAIN. 

3957
03:29:34,160 --> 03:29:43,840
NEXT IS DR. JUN ON IMMUNE CELL 

3958
03:29:43,840 --> 03:29:45,200
AND DISFUNCTION. 

3959
03:29:45,200 --> 03:29:46,560
>> CAN YOU HEAR ME OKAY. 

3960
03:29:46,560 --> 03:29:47,640
>> YES, SIR. 

3961
03:29:47,640 --> 03:29:49,160
>> THANK YOU SO MUCH FOR GIVING 

3962
03:29:49,160 --> 03:29:50,640
ME OPPORTUNITY TO PRESENT OUR 

3963
03:29:50,640 --> 03:29:51,680
DATA HERE. 

3964
03:29:51,680 --> 03:29:53,200
THIS IS A WONDERFUL WORKSHOP. 

3965
03:29:53,200 --> 03:29:56,040
SO TODAY I'D LIKE TO TELL YOU 

3966
03:29:56,040 --> 03:29:58,760
ABOUT THIS IDENTIFICATION OF 

3967
03:29:58,760 --> 03:30:08,880
IMMUNE MODULETARY AND FOCUS ON T

3968
03:30:08,880 --> 03:30:09,120
CELLS. 

3969
03:30:09,120 --> 03:30:14,720
ON T CELLS FOLLOWING TALKING I'M

3970
03:30:14,720 --> 03:30:18,960
GOING TO FOCUS ON-70 CELLS 

3971
03:30:18,960 --> 03:30:22,160
INVOLVED IN HOSTING IMMUNE 

3972
03:30:22,160 --> 03:30:25,320
RESPONSE AGAINST EXPRESS 

3973
03:30:25,320 --> 03:30:27,400
BACTERIA BUT THOSE INVOLVED IN 

3974
03:30:27,400 --> 03:30:30,360
DIFFERENT TYPES OF AUTO 

3975
03:30:30,360 --> 03:30:30,720
INFLAMMATION. 

3976
03:30:30,720 --> 03:30:33,760
THE UNIQUE FEATURE OF THE CELLS 

3977
03:30:33,760 --> 03:30:36,880
IS IT'S PROGRAMMED KEY 

3978
03:30:36,880 --> 03:30:39,560
TRANSCRIPTION PROGRAM IS 

3979
03:30:39,560 --> 03:30:41,400
TRANSCRIPTION FACTOR WHICH 

3980
03:30:41,400 --> 03:30:45,560
HAPPENS THROB A RO GAMMA T WHICH

3981
03:30:45,560 --> 03:30:51,680
HAS A CONTROL WITH LIGON. 

3982
03:30:51,680 --> 03:30:56,040
MANY YEARS AGO WE WANTED TO 

3983
03:30:56,040 --> 03:31:00,880
IDENTIFY AN INHIBITOR THAT CAN 

3984
03:31:00,880 --> 03:31:05,360
BLOCK THE CELLS BY BINDING TO 

3985
03:31:05,360 --> 03:31:19,560
GAMMA LIGON, FROM THIS APPROACH 

3986
03:31:19,560 --> 03:31:23,000
WE ARE ABLE TO IDENTIFY PLANT 

3987
03:31:23,000 --> 03:31:26,760
DERIVED CARDIAC TOXIN AS SHOWN 

3988
03:31:26,760 --> 03:31:30,360
HERE THAT INTERACT WITH RA GAMMA

3989
03:31:30,360 --> 03:31:33,800
T AND SUPPRESSES TRANSCRIPTION 

3990
03:31:33,800 --> 03:31:34,120
ACTIVITY.  

3991
03:31:34,120 --> 03:31:36,120
WHEN WE ADD TO THE CULTURE WE 

3992
03:31:36,120 --> 03:31:40,760
ARE ABLE TO FIND THAT INHIBITS 

3993
03:31:40,760 --> 03:31:42,040
SUBL DIFFERENTIATION COMPARED TO

3994
03:31:42,040 --> 03:31:45,680
A CONTROL, WITHOUT AFFECTING T 

3995
03:31:45,680 --> 03:31:50,520
CELL ABILITY TO BECOME ANOTHER T

3996
03:31:50,520 --> 03:31:54,720
AFFECTOR CELLS. 

3997
03:31:54,720 --> 03:31:57,720
SIGNS THEIR PRESENTED IN THE GUT

3998
03:31:57,720 --> 03:32:00,000
AND WE THOUGHT PERHAPS 

3999
03:32:00,000 --> 03:32:03,160
MICROBIOTA HAVE A ABILITY TO 

4000
03:32:03,160 --> 03:32:06,280
CONTROL FUNCTION BY SECRETING 

4001
03:32:06,280 --> 03:32:08,920
INTO THE METABOLITES THAT MAY 

4002
03:32:08,920 --> 03:32:13,160
ACT ON RO GAMMA  T JUST LIKE 

4003
03:32:13,160 --> 03:32:15,000
INYOU BEHINDIVE FUNCTION SO 

4004
03:32:15,000 --> 03:32:18,800
BASICALLY THE QUESTION IS CAN WE

4005
03:32:18,800 --> 03:32:22,600
IDENTIFY NATURAL BACTERIA 

4006
03:32:22,600 --> 03:32:22,960
METABOLITES. 

4007
03:32:22,960 --> 03:32:26,720
SO FIND THESE MOLECULES WE 

4008
03:32:26,720 --> 03:32:38,120
DECIDED TO FOCUS ON BIO AS SAY 

4009
03:32:38,120 --> 03:32:41,560
BIASES EVEN THOUGH HOSTED IN THE

4010
03:32:41,560 --> 03:32:46,960
LIVER WHEN BHE GOT THE BACTERIA 

4011
03:32:46,960 --> 03:32:50,160
TRANSFORMATION SO BIOAS SAY CAN 

4012
03:32:50,160 --> 03:32:53,480
BE METABOLITES AND HAVE A 

4013
03:32:53,480 --> 03:32:56,320
STRUCTURE SIMILARITY TO THOSE OF

4014
03:32:56,320 --> 03:33:01,720
KNOWN LIGONS THAT INCLUDING THE 

4015
03:33:01,720 --> 03:33:16,960
SPECIFIC INHIBITOR. 

4016
03:33:16,960 --> 03:33:47,000
THESE ARE THE STRUCTURAL SO WE 

4017
03:33:47,000 --> 03:33:49,920
WANTED TO TEST HER HIGH 

4018
03:33:49,920 --> 03:33:53,120
HYPOTHESIS THAT THIS ACTS AT RO 

4019
03:33:53,120 --> 03:33:55,360
GAMMA INHIBITOR. 

4020
03:33:55,360 --> 03:33:59,720
SO, TO IDENTIFY SUCH A MOLECULE 

4021
03:33:59,720 --> 03:34:02,480
WE COLLABORATED AND COLLECTED 

4022
03:34:02,480 --> 03:34:07,080
VARIOUS PRIMARY BIOAS SAYS AND 

4023
03:34:07,080 --> 03:34:09,480
RAN A VERY SMALL SCALE CHEMICAL 

4024
03:34:09,480 --> 03:34:13,960
SCREEN IN THIS CASE INSTEAD OF 

4025
03:34:13,960 --> 03:34:18,320
USING WE USE A PRIMARY T CELL SO

4026
03:34:18,320 --> 03:34:26,120
WE . . .  AS CONTROL AND DURING 

4027
03:34:26,120 --> 03:34:29,160
THIS PROCESS WE ADDED INDIVIDUAL

4028
03:34:29,160 --> 03:34:29,960
BOW AS SAY. 

4029
03:34:29,960 --> 03:34:33,560
SO FROM THIS APPROACH WE WERE 

4030
03:34:33,560 --> 03:34:46,560
ABLE TO IDENTIFY TWO DYNA DRIVE 

4031
03:34:46,560 --> 03:34:50,760
WITHOUT AFFECTING 

4032
03:34:50,760 --> 03:34:52,320
DIFFERENTIATION BUT WE FOUND 

4033
03:34:52,320 --> 03:35:00,080
THAT ENHANCER SO IF I SHOW YOU 

4034
03:35:00,080 --> 03:35:03,840
PRELIMINARY RAW DATA WE FOUND 

4035
03:35:03,840 --> 03:35:42,120
THAT . . .  

4036
03:35:42,120 --> 03:35:45,800
>> AND THEN WHEN WE ADD THIS 

4037
03:35:45,800 --> 03:35:49,440
MOLECULE TO CULTURE, INDIVIDUAL 

4038
03:35:49,440 --> 03:35:53,960
CULTURE DIFFERENTIATION NOT OWL 

4039
03:35:53,960 --> 03:35:56,840
MOLECULE SUPPRESS 

4040
03:35:56,840 --> 03:35:57,240
DIFFERENTIATION. 

4041
03:35:57,240 --> 03:36:02,400
SO WHEN WE DID RNA ANALYSIS WITH

4042
03:36:02,400 --> 03:36:04,920
WIDE TYPE T CELLS IN THE CULTURE

4043
03:36:04,920 --> 03:36:06,640
AND COMPARED AND FOUND THAT IT'S

4044
03:36:06,640 --> 03:36:09,360
A GENE EXPRESSION CHANGES ARE 

4045
03:36:09,360 --> 03:36:12,960
VERY SIMILAR TO THOSE CHANGES IN

4046
03:36:12,960 --> 03:36:22,360
TH

4047
03:36:22,360 --> 03:36:26,720
THIS, LIKELY TO BE A MAJOR 

4048
03:36:26,720 --> 03:36:28,160
TARGET OF IT. 

4049
03:36:28,160 --> 03:36:33,480
IN VIVO WHETHER WE INDUCED THE 

4050
03:36:33,480 --> 03:36:38,000
DIFFERENTIATION BY FEEDING MICE 

4051
03:36:38,000 --> 03:36:49,000
WITH-17 BACTERIA WE SUBJECT 

4052
03:36:49,000 --> 03:36:51,280
THESE MICE TO DIET AND THEY'RE 

4053
03:36:51,280 --> 03:37:02,280
LED TO LEVEL OF T CELL IN VIVO 

4054
03:37:02,280 --> 03:37:04,960
WITH MICE AS WELL SO FROM THIS 

4055
03:37:04,960 --> 03:37:08,440
APPROACH WE ARE ABLE TO ABLE TO 

4056
03:37:08,440 --> 03:37:12,960
FIND DIFFERENT SHAKES WITH RO, 

4057
03:37:12,960 --> 03:37:15,720
GAMMA 2 AND BASICALLY FUNCTION 

4058
03:37:15,720 --> 03:37:16,040
INHIBITOR. 

4059
03:37:16,040 --> 03:37:19,880
I DON'T HAVE A TIME TO ALL THE 

4060
03:37:19,880 --> 03:37:22,320
DATA BUT THIS PUBLISHED WORK SO 

4061
03:37:22,320 --> 03:37:24,960
JUST GIVE YOU THIS ONE DATA 

4062
03:37:24,960 --> 03:37:28,200
THERE, SO THIS DATA INCREDIBLE 

4063
03:37:28,200 --> 03:37:32,320
SPECIFICITY OF METABOLITE. 

4064
03:37:32,320 --> 03:37:38,040
IN THIS CASE ALMOST ALL FOUR 

4065
03:37:38,040 --> 03:37:48,480
ISOMARS WE USE AN EXPRESSION AS 

4066
03:37:48,480 --> 03:37:52,960
A READ OUT AND FOUND THAT IT'S 

4067
03:37:52,960 --> 03:37:55,760
ONLY RELATED MOLECULE CAN 

4068
03:37:55,760 --> 03:37:56,560
INCREASE DIFFERENCES SHAKES 

4069
03:37:56,560 --> 03:37:58,000
AGAIN HIGHLIGHTING THE 

4070
03:37:58,000 --> 03:38:00,040
INCREDIBLE SPECIFICITY OF THIS 

4071
03:38:00,040 --> 03:38:01,320
VIRUS. 

4072
03:38:01,320 --> 03:38:07,200
SO, FROM H DATA WE ARE ABLE TO 

4073
03:38:07,200 --> 03:38:11,360
FIND TRANSFORMED INTO TWO 

4074
03:38:11,360 --> 03:38:16,520
DIFFERENT MOLECULES THAT GET TO 

4075
03:38:16,520 --> 03:38:21,640
THE IMMUNE CELL T CELLS IN VIVO 

4076
03:38:21,640 --> 03:38:24,640
AND EITHER BY SUPPRESSING BY 

4077
03:38:24,640 --> 03:38:28,280
GAMMA 2 OR ENHANCING REGAILIA 

4078
03:38:28,280 --> 03:38:34,920
FRIDAY T CELL BY STIMULATING OR 

4079
03:38:34,920 --> 03:38:38,920
CHANGES AND BIAS BASICALLY 

4080
03:38:38,920 --> 03:38:40,160
SUPPRESSING INFLAMMATION. 

4081
03:38:40,160 --> 03:38:47,760
SO, AFTER WE GOT THIS DATA WE 

4082
03:38:47,760 --> 03:38:49,840
WANTED TO FIND THE BACTERIA THAT

4083
03:38:49,840 --> 03:38:53,040
NEED YATES THIS PROCESS. 

4084
03:38:53,040 --> 03:38:57,960
SO WE WORKED WITH HARVARD 

4085
03:38:57,960 --> 03:39:00,360
MEDICAL SCHOOL AND SHE BASICALLY

4086
03:39:00,360 --> 03:39:04,440
ICE LATHE A THOUSAND BACTERIA 

4087
03:39:04,440 --> 03:39:13,160
COLONIES FROM TWO  SAMPLES OF 

4088
03:39:13,160 --> 03:39:17,960
COLITIS PATIENTS AND ANDED . . .

4089
03:39:17,960 --> 03:39:21,360
ACID AND AMONG THE MANY BACTERIA

4090
03:39:21,360 --> 03:39:23,840
WAS ABLE TO IDENTIFY SEVERAL 

4091
03:39:23,840 --> 03:39:25,720
BACTERIA AND THE ABILITY TO 

4092
03:39:25,720 --> 03:39:31,840
GENERATE CELLS FROM LCA SO 

4093
03:39:31,840 --> 03:39:34,160
THAT'S WHAT WE FOCUSED ON FOR 

4094
03:39:34,160 --> 03:39:37,160
THE FOLLOWUP ANALYSIS TO HAVE AN

4095
03:39:37,160 --> 03:39:42,360
ENZYME AND WE THINK THIS ENGINE 

4096
03:39:42,360 --> 03:39:45,160
NEED YATES THIS TRANSFORMATION. 

4097
03:39:45,160 --> 03:39:48,960
HOWEVER, THERE'S NO GENETIC 

4098
03:39:48,960 --> 03:39:51,360
MANIPULATION AVAILABLE, SO WE 

4099
03:39:51,360 --> 03:39:59,400
COLLECT IT AS A HOW MANY -- 

4100
03:39:59,400 --> 03:40:01,400
HUMAN ISOLATE WHY THOSE ISOLATED

4101
03:40:01,400 --> 03:40:07,280
DO NOT HAVE THIS ENGINE CAN 

4102
03:40:07,280 --> 03:40:12,560
GENERATE SO WE SHOW THAT THIS IS

4103
03:40:12,560 --> 03:40:16,960
EXPRESSING THIS ENGINE CAN 

4104
03:40:16,960 --> 03:40:20,480
PRESENCE OF THERE ENZYME 

4105
03:40:20,480 --> 03:40:46,280
CORRELATES WITH PRODUCTION OF 

4106
03:40:46,280 --> 03:40:51,040
THE ENZYME INPUT AND FOR THE 

4107
03:40:51,040 --> 03:40:52,960
INHIBITION OF CELLS 

4108
03:40:52,960 --> 03:40:54,880
DIFFERENTIATION. 

4109
03:40:54,880 --> 03:41:01,160
SO WE SHOW THAT THE COLONIZATION

4110
03:41:01,160 --> 03:41:07,240
IS SUFFICIENT TO PRODUCE T CELLS

4111
03:41:07,240 --> 03:41:10,160
HOWEVER WHEN WE COLONIZE I DOES 

4112
03:41:10,160 --> 03:41:13,280
NOT HAVE THIS ENZYME, WE NO 

4113
03:41:13,280 --> 03:41:17,160
LONGER ABLE TO DETECT THIS 

4114
03:41:17,160 --> 03:41:19,680
PRODUCTION. 

4115
03:41:19,680 --> 03:41:22,080
FUNCTIONLY WE SHOW THAT IT'S 

4116
03:41:22,080 --> 03:41:26,680
FEEDING MICE WITH THE LCA THAT 

4117
03:41:26,680 --> 03:41:29,400
DOESN'T AFFECT DIFFERENTIATION 

4118
03:41:29,400 --> 03:41:32,400
SO THIS PARTICULAR CASE WE ARE 

4119
03:41:32,400 --> 03:41:37,640
INDUCING THE CELL INJECTIONSING 

4120
03:41:37,640 --> 03:41:41,560
MICE WITH CIPRO FAST FOR AND 

4121
03:41:41,560 --> 03:41:45,720
CORRELATE THE . . .  AND DON'T 

4122
03:41:45,720 --> 03:41:48,040
SEE CORRELATION. 

4123
03:41:48,040 --> 03:41:51,640
HOWEVER WHEN WE REPEAT THE SAME 

4124
03:41:51,640 --> 03:41:55,120
EXPERIMENT COLONIZED WITH . . . 

4125
03:41:55,120 --> 03:41:57,040
BACTERIA WE ARE ABLE TO PROTECT 

4126
03:41:57,040 --> 03:42:00,880
THOSE MICE THAT WITH HIGHER 

4127
03:42:00,880 --> 03:42:05,360
LEVEL OF . . .  WHICH I DIDN'T 

4128
03:42:05,360 --> 03:42:09,280
HAVE TIME TO TELL YOU ABOUT IT, 

4129
03:42:09,280 --> 03:42:16,240
WE SAW THERE'S A LEVEL PRESENCE 

4130
03:42:16,240 --> 03:42:19,120
OF THIS BACTERIA WHICH HAS THE 

4131
03:42:19,120 --> 03:42:24,120
ABILITY TO GENERATE INHIBITOR 

4132
03:42:24,120 --> 03:42:28,120
LCA IT CAN REGULATE 

4133
03:42:28,120 --> 03:42:32,200
DIFFERENTIATION IN MOUSE IN 

4134
03:42:32,200 --> 03:42:32,400
VIVO. 

4135
03:42:32,400 --> 03:42:37,720
>> DR. HUH YOU HAVE A COME MORE 

4136
03:42:37,720 --> 03:42:38,080
MINUTES. 

4137
03:42:38,080 --> 03:42:40,720
>> WE COORDINATE WITH PUBLIC 

4138
03:42:40,720 --> 03:42:44,600
HEALTH AND LOOK AT THE RELATIVE 

4139
03:42:44,600 --> 03:42:47,160
LEVEL OF VARIOUS VIRUS AND HOW 

4140
03:42:47,160 --> 03:42:49,160
THEY'RE CONTROLLED AND THIS IS A

4141
03:42:49,160 --> 03:42:52,720
VERY BUSY SLIDE BUT BASICALLY AS

4142
03:42:52,720 --> 03:42:54,760
YOU CAN SEE MOST OF THE BIOPSIES

4143
03:42:54,760 --> 03:42:56,400
WE LOOK AT THE LEVEL IS 

4144
03:42:56,400 --> 03:42:57,280
COMPARABLE. 

4145
03:42:57,280 --> 03:43:00,320
IT DOESN'T MATTER WHETHER 

4146
03:43:00,320 --> 03:43:05,080
THEY'RE LIKE IV PATIENT OR 

4147
03:43:05,080 --> 03:43:10,800
HEALTHY HOWEVER WE LOOK AT 

4148
03:43:10,800 --> 03:43:13,760
BIO-ASSAY WE FOUND THEIR LEVELS 

4149
03:43:13,760 --> 03:43:18,920
ARE DECREASED IN PATIENT WITH 

4150
03:43:18,920 --> 03:43:21,680
IBD SO NEVER TO BE ASSOCIATED 

4151
03:43:21,680 --> 03:43:23,600
WITH INFLAMMATORY CONDITION. 

4152
03:43:23,600 --> 03:43:27,000
SO BASED ON FROM THESE DAD WE 

4153
03:43:27,000 --> 03:43:30,560
ARE ABLE TO SHOW IDENTIFY THIS 

4154
03:43:30,560 --> 03:43:34,440
EXAMPLE WHERE ONE . . .  CAN BE 

4155
03:43:34,440 --> 03:43:38,520
FURTHER MODIFIED THROUGH THE 

4156
03:43:38,520 --> 03:43:42,560
INTRODUCTION OF BACTERIA . . .  

4157
03:43:42,560 --> 03:43:46,560
AND THEN YOU KNOW, SO KIND OF 

4158
03:43:46,560 --> 03:43:50,520
AROUND THE SAME TIME A SIMILAR 

4159
03:43:50,520 --> 03:43:52,560
REPORT WAS KIND OF A PAPER 

4160
03:43:52,560 --> 03:43:54,280
FINDING OR REPORTED FROM OTHER 

4161
03:43:54,280 --> 03:44:04,360
GROUPS IN THAT THEY ALL FOUND 

4162
03:44:04,360 --> 03:44:07,920
AND THE REAL YINTING FINDING IS 

4163
03:44:07,920 --> 03:44:12,560
THAT ALL THIS VIRUS IS SEEM TO 

4164
03:44:12,560 --> 03:44:16,800
WORK ON RECEPTORS SO SUGGESTING 

4165
03:44:16,800 --> 03:44:21,240
THE COMPLEX NATURE OF THIS 

4166
03:44:21,240 --> 03:44:23,160
REGULAR MECHANISM AND IS VERY 

4167
03:44:23,160 --> 03:44:28,040
INTERESTING FINDING WAS MADE BY 

4168
03:44:28,040 --> 03:44:33,920
HONDA GROUP IN JAPAN AND NOTICED

4169
03:44:33,920 --> 03:44:38,120
IDENTIFIED HIGHLY PRESENTING THE

4170
03:44:38,120 --> 03:44:42,320
CENTENARIAN PATIENT SO THE 

4171
03:44:42,320 --> 03:44:43,400
IMPORTANCE OF INTRODUCTION IN 

4172
03:44:43,400 --> 03:44:44,000
HUMAN HEALTH. 

4173
03:44:44,000 --> 03:44:47,280
I STOP HERE, ALL THIS WORK IS 

4174
03:44:47,280 --> 03:44:52,640
DONE BY HIGHLY TALENTED FELLOW 

4175
03:44:52,640 --> 03:44:55,560
IN MY LAB, AND ALL THIS WORK IS 

4176
03:44:55,560 --> 03:44:57,760
REALLY MADE POSSIBLE THROUGH A 

4177
03:44:57,760 --> 03:44:58,960
WONDERFUL COLLABORATION WITH 

4178
03:44:58,960 --> 03:45:00,400
MANY WONDERFUL SCIENTISTS AND 

4179
03:45:00,400 --> 03:45:06,360
PARTICULARLY A BIG SHOUT TO THE 

4180
03:45:06,360 --> 03:45:08,240
STAFF MS AND CONTRIBUTING TO 

4181
03:45:08,240 --> 03:45:10,040
MAKE THESE FINDINGS SO I WANT TO

4182
03:45:10,040 --> 03:45:11,760
STOP HERE AND THANK YOU VERY 

4183
03:45:11,760 --> 03:45:12,120
MUCH. 

4184
03:45:12,120 --> 03:45:17,160
>> THANK YOU DR. HUH FOR YOUR 

4185
03:45:17,160 --> 03:45:18,320
STIMULATING TALK. 

4186
03:45:18,320 --> 03:45:21,240
IT'S REALLY A VERY STIMULATING 

4187
03:45:21,240 --> 03:45:21,600
TALK. 

4188
03:45:21,600 --> 03:45:28,800
WE MOVE ON TO DR. AMIR FROM 

4189
03:45:28,800 --> 03:45:29,840
UNIVERSITY OF CALIFORNIA SAN 

4190
03:45:29,840 --> 03:45:33,600
DIEGO, TALKING ABOUT THE 

4191
03:45:33,600 --> 03:45:35,360
MICROBIOME AND TIME. 

4192
03:45:35,360 --> 03:45:38,200
AND THIS WILL BE THE LAST PART 

4193
03:45:38,200 --> 03:45:40,720
OF OUR AFTERNOON SESSION USING 

4194
03:45:40,720 --> 03:45:42,240
ENGINEERED BACTERIA TO 

4195
03:45:42,240 --> 03:45:46,160
UNDERSTAND THE MICROBIOME AND 

4196
03:45:46,160 --> 03:45:47,560
CIRCADIAN RHYTHM AND 

4197
03:45:47,560 --> 03:45:47,960
RELATIONSHIPS. 

4198
03:45:47,960 --> 03:45:50,480
>> AMIR. 

4199
03:45:50,480 --> 03:45:52,320
>> CAN YOU HEAR ME? 

4200
03:45:52,320 --> 03:45:52,560
GREAT. 

4201
03:45:52,560 --> 03:45:54,000
THANK YOU FOR THAT INTRODUCTION 

4202
03:45:54,000 --> 03:45:56,800
AND ORGANIZING SUCH AN 

4203
03:45:56,800 --> 03:45:58,000
OUTSTANDING CONFERENCE. 

4204
03:45:58,000 --> 03:46:01,360
DEFINITELY VERY EXCITING TO HEAR

4205
03:46:01,360 --> 03:46:06,080
MY COLLEAGUES TALK. 

4206
03:46:06,080 --> 03:46:08,120
AND I DO HAVE SOME DISCLOSURES. 

4207
03:46:08,120 --> 03:46:09,800
IN PARTICULAR SOME OF THE 

4208
03:46:09,800 --> 03:46:12,960
ENGINEERED BACTERIA WORK THAT 

4209
03:46:12,960 --> 03:46:15,600
I'LL BE DESCRIBING HAVE BEEN 

4210
03:46:15,600 --> 03:46:17,560
LICENSED THROUGH A COMPANY 

4211
03:46:17,560 --> 03:46:18,560
CALLED 

4212
03:46:18,560 --> 03:46:21,280
[NAME] BIOTHERAPEUTICS AN SINCE 

4213
03:46:21,280 --> 03:46:23,560
THIS IS TALKING TO A 

4214
03:46:23,560 --> 03:46:25,280
NON-CIRCADIAN BIOLOGY GROUP IT'S

4215
03:46:25,280 --> 03:46:27,320
WORTH BACKING UP TO DISCUSS HOW 

4216
03:46:27,320 --> 03:46:29,600
THE ROTATION OF THE EARTH WHICH 

4217
03:46:29,600 --> 03:46:32,400
CAUSES CHANGES IN TEMPERATURE IS

4218
03:46:32,400 --> 03:46:35,920
A VITAL ENVIRONMENTAL CUE. 

4219
03:46:35,920 --> 03:46:38,600
ANIMALS FROM SIGN A BACTERIA TO 

4220
03:46:38,600 --> 03:46:40,400
MAN ALWAYS HAVE EVOLVED 

4221
03:46:40,400 --> 03:46:41,880
MECHANISMS TO TAKE ADVANTAGE OF 

4222
03:46:41,880 --> 03:46:43,400
THESE CHANGES DURING THE DAY, 

4223
03:46:43,400 --> 03:46:45,600
AND AS YOU CAN IMAGINE, AN 

4224
03:46:45,600 --> 03:46:46,920
ANIMAL THAT IS ABLE TO PREDICT 

4225
03:46:46,920 --> 03:46:48,560
WHEN IT'S GOING TO BE DARK OUT 

4226
03:46:48,560 --> 03:46:52,080
OR WITH IT'S GOING TO BE COLD, 

4227
03:46:52,080 --> 03:46:53,360
WILL HAVE AN ADVANTAGE OVER ONES

4228
03:46:53,360 --> 03:46:55,680
THAT DO NOT HAVE OR CANNOT MAKE 

4229
03:46:55,680 --> 03:46:57,200
THOSE PREDICTIONS AND WILL NOT 

4230
03:46:57,200 --> 03:46:58,760
KNOW WHEN IT'S GOOD TO GO OUT 

4231
03:46:58,760 --> 03:47:02,440
AND WITH IT'S TIME TO GO HOME TO

4232
03:47:02,440 --> 03:47:03,760
THE NEST. 

4233
03:47:03,760 --> 03:47:08,160
ABOUT 45 PERCENT OF ALL GENES 

4234
03:47:08,160 --> 03:47:12,360
ACROSS ORGANS ON THE LATE IN A 

4235
03:47:12,360 --> 03:47:15,400
24-HOUR PERIOD AN AS CAN YOU SEE

4236
03:47:15,400 --> 03:47:17,800
BY THE STUD BY 

4237
03:47:17,800 --> 03:47:19,240
[NAME] ET AL THEY ARE INVOLVED 

4238
03:47:19,240 --> 03:47:20,680
IN DISEASES AND WILL BE OFTEN 

4239
03:47:20,680 --> 03:47:23,640
THE TARGET OF MEDICATIONS, IN 

4240
03:47:23,640 --> 03:47:29,760
PARTICULARLY, METABOLISM IS A 

4241
03:47:29,760 --> 03:47:30,360
IMPORTA

4242
03:47:30,360 --> 03:47:31,400
IMPORTANTER IS KADIAN SYSTEM AND

4243
03:47:31,400 --> 03:47:34,560
ABOUT 80 PERCENT OF GENES ON THE

4244
03:47:34,560 --> 03:47:36,520
LATE IN A 24 HOUR PERIOD.  

4245
03:47:36,520 --> 03:47:41,000
WHEN WE TALK ABOUT CIRCADIAN 

4246
03:47:41,000 --> 03:47:43,440
RUMSFELD PEOPLE GET IMAGES OF 

4247
03:47:43,440 --> 03:47:47,800
JETLAG OR LACK OF SLEEP BUT WE 

4248
03:47:47,800 --> 03:47:51,040
ARE TALKING ABOUT AUTONOMOUS 

4249
03:47:51,040 --> 03:47:53,440
CIRCADIAN PROTEINS TO HELP EACH 

4250
03:47:53,440 --> 03:47:54,880
SUBTLTIES PATE WHAT IT SHOULD BE

4251
03:47:54,880 --> 03:47:57,960
DOING OR MACHINERY UP OR DOWN 

4252
03:47:57,960 --> 03:48:05,120
REGULATING BASED ON,  EXTERNAL 

4253
03:48:05,120 --> 03:48:05,520
EVENTS. 

4254
03:48:05,520 --> 03:48:08,840
THE REASON WHY THESE SYSTEMS ARE

4255
03:48:08,840 --> 03:48:10,880
IMPORTANT IS THEY COORDINATE 

4256
03:48:10,880 --> 03:48:13,000
DISTANCE IN TISSUES AND ACROSS 

4257
03:48:13,000 --> 03:48:16,200
MULTIPLE SYSTEMS, FIZZ LOGICAL 

4258
03:48:16,200 --> 03:48:18,600
PROPHECIES WITH EACH OTHER. 

4259
03:48:18,600 --> 03:48:20,040
WHEN I STARTED BECOMING 

4260
03:48:20,040 --> 03:48:23,840
INTERESTED IN CIRCADIAN BIOLOGY,

4261
03:48:23,840 --> 03:48:25,960
ONE OF THE MAIN QUESTIONS THAT 

4262
03:48:25,960 --> 03:48:28,640
CIRCADIAN BIOLOGISTS HAD WAS HOW

4263
03:48:28,640 --> 03:48:30,560
DOES LIGHT PERCEPTION OR SIGNALS

4264
03:48:30,560 --> 03:48:32,560
THAT WE GET FROM OUR RETINA THAT

4265
03:48:32,560 --> 03:48:35,760
GOES TO OUR BRAIN LEAD TO 

4266
03:48:35,760 --> 03:48:38,240
CIRCADIAN ON THE LEGISLATION IN 

4267
03:48:38,240 --> 03:48:39,720
THE PERIPHERAL ORGANS AND THERE 

4268
03:48:39,720 --> 03:48:44,040
WAS PURPORTED TO BE THIS NEURAL 

4269
03:48:44,040 --> 03:48:46,640
HUMERAL MECHANISM THAT WE HAVE 

4270
03:48:46,640 --> 03:48:48,640
NOT IDENTIFIED POSSIBLY INVOLVED

4271
03:48:48,640 --> 03:48:52,240
IN AUTONOMIC NERVOUS SYSTEM OR 

4272
03:48:52,240 --> 03:48:53,440
HORMONES WE HAD NOT YET 

4273
03:48:53,440 --> 03:48:57,000
IDENTIFIED THAT HELPED THE CNS 

4274
03:48:57,000 --> 03:48:59,000
CONTROL PERIPHERAL RHYTHM IN 

4275
03:48:59,000 --> 03:49:03,000
LUNGS KIDNEYS INTESTINES AND 

4276
03:49:03,000 --> 03:49:04,640
LIVER, HOWEVER OVER THE LAST 6 

4277
03:49:04,640 --> 03:49:07,160
YEARS WHAT IS CRYSTALIZING IS 

4278
03:49:07,160 --> 03:49:12,760
THE MICROBIOME THAT'S REQUIRED 

4279
03:49:12,760 --> 03:49:14,920
FOR LIGHT TO ENTRAIN THOSE 

4280
03:49:14,920 --> 03:49:17,960
CLOCKS, AND THAT IT CAN ALSO 

4281
03:49:17,960 --> 03:49:18,800
MODULATED OTHER PERIPHERAL 

4282
03:49:18,800 --> 03:49:21,880
ORGANS SUCH AS THE KIDNEYS AND 

4283
03:49:21,880 --> 03:49:24,160
THE SPLEEN FOR EXAMPLE, AND THAT

4284
03:49:24,160 --> 03:49:27,160
REALLY WHAT'S HAPPENING IS THAT 

4285
03:49:27,160 --> 03:49:29,760
THE BRAIN IS INFLUENCING THE 

4286
03:49:29,760 --> 03:49:33,480
TIMING OF THE OUR FEEDING AND 

4287
03:49:33,480 --> 03:49:35,720
ENTRAINING THE CLOCK THROUGH 

4288
03:49:35,720 --> 03:49:37,440
NEAT RENT INTAKE AN ALSO THE 

4289
03:49:37,440 --> 03:49:41,120
PRODUCTION OF SECONDARY 

4290
03:49:41,120 --> 03:49:42,680
METABOLITES. 

4291
03:49:42,680 --> 03:49:48,160
SO THESE MICROBAL METABOLITES 

4292
03:49:48,160 --> 03:49:49,680
ARE ENTRAINING AGENTS. 

4293
03:49:49,680 --> 03:49:52,560
WE DON'T UNDERSTAND HOW YET. 

4294
03:49:52,560 --> 03:49:55,480
WE HAVE CANDIDATES IN MODIFIED 

4295
03:49:55,480 --> 03:49:58,040
BILE ACID IS AS BEING SECONDSARY

4296
03:49:58,040 --> 03:49:59,960
METABOLITES AND THIS IS AN AREA 

4297
03:49:59,960 --> 03:50:02,000
OF ACTIVE INVESTIGATION. 

4298
03:50:02,000 --> 03:50:04,840
GOING BACK TO SIR KADE YUM 

4299
03:50:04,840 --> 03:50:07,560
RHYTHM AND METABOLISM THE 

4300
03:50:07,560 --> 03:50:08,680
RELATIONSHIP BETWEEN THESE TWO 

4301
03:50:08,680 --> 03:50:11,360
BECAME VERY SALIENT WHEN 

4302
03:50:11,360 --> 03:50:14,640
MUTATIONS OF CIRCADIAN 

4303
03:50:14,640 --> 03:50:17,480
REGULATORS HAVE LED TO THIS 

4304
03:50:17,480 --> 03:50:19,960
METABOLIC MODEL SO BASICALLY 

4305
03:50:19,960 --> 03:50:23,400
EVERY CLOCK EVERY MUTANT OF A 

4306
03:50:23,400 --> 03:50:27,280
CLOCK PROTEIN THAT IS THIS 

4307
03:50:27,280 --> 03:50:29,880
METABOLIC PHENOTYPE. 

4308
03:50:29,880 --> 03:50:30,320
AND 

4309
03:50:30,320 --> 03:50:31,960
[NAME] SHOWS THAT CLOCK 

4310
03:50:31,960 --> 03:50:34,400
MUTATIONS IN HUMANS ARE 

4311
03:50:34,400 --> 03:50:36,360
ASSOCIATED WITH DIABETES AND 

4312
03:50:36,360 --> 03:50:40,320
OBESITY AND NOT SURE IF THERE'S 

4313
03:50:40,320 --> 03:50:42,080
THERAPEUTIC POTENTIAL THUS FAR. 

4314
03:50:42,080 --> 03:50:43,600
OTHER THING INTERESTING EVERY 

4315
03:50:43,600 --> 03:50:50,680
MODEL OBESITY HAS SOME OTHER SIR

4316
03:50:50,680 --> 03:50:53,680
KADE YUM RHYTHM PROBLEM, BEST 

4317
03:50:53,680 --> 03:50:54,520
EXAMPLE MICE MORE THAN DOUBLED 

4318
03:50:54,520 --> 03:50:57,080
THE AMOUNT OF FOOD INTAKE AND 

4319
03:50:57,080 --> 03:51:00,200
DURING THE PERIOD WHEN THEY'RE 

4320
03:51:00,200 --> 03:51:03,360
SUPPOSED TO REST AND THEY 

4321
03:51:03,360 --> 03:51:07,400
ESSENTIALLY SUPPRESS CALORIE 

4322
03:51:07,400 --> 03:51:09,360
INTAKE AN THAT IS NOT A BIG PART

4323
03:51:09,360 --> 03:51:09,960
OF THIS. 

4324
03:51:09,960 --> 03:51:14,360
WE HAVE DONE A STUDY TO SHOW SIR

4325
03:51:14,360 --> 03:51:16,240
KA

4326
03:51:16,240 --> 03:51:19,520
KADIAN FLUCTUATIONS IN THE GUT 

4327
03:51:19,520 --> 03:51:21,160
BIOME BUT NICE EAT DURING THE 

4328
03:51:21,160 --> 03:51:22,160
NOCTURNAL PERIOD SO THIS IS JUST

4329
03:51:22,160 --> 03:51:24,840
A TRACING OF A MOUSE FEEDING 

4330
03:51:24,840 --> 03:51:26,520
PATTERN AND AS YOU CAN CAN SEE 

4331
03:51:26,520 --> 03:51:28,080
DURING THE NOCTURNAL PERIOD THEY

4332
03:51:28,080 --> 03:51:30,160
EAT MORE AND WE SEED A CHANGE IN

4333
03:51:30,160 --> 03:51:32,960
THE GUT MICROBIOME THAT IS IN 

4334
03:51:32,960 --> 03:51:35,320
LINE WITH THAT WHERE THERE'S AN 

4335
03:51:35,320 --> 03:51:37,240
INCREASE AND DECREASE IN 

4336
03:51:37,240 --> 03:51:38,560
BACTERIA EATING SPECIES BUT 

4337
03:51:38,560 --> 03:51:40,320
DURING THE RELATIVE FAST WHEN 

4338
03:51:40,320 --> 03:51:41,400
THEY'RE SLEEPING DURING THE 

4339
03:51:41,400 --> 03:51:43,480
LIGHT PERIOD WE SEE AND 

4340
03:51:43,480 --> 03:51:46,520
COMPLETELY ALTER FLUCTUATION. 

4341
03:51:46,520 --> 03:51:50,160
DIET INDUCED OBESITY MICE ARE 

4342
03:51:50,160 --> 03:51:52,920
CONSUMEING THE SAME AMOUNT OF 

4343
03:51:52,920 --> 03:51:55,560
FOOD NIGHT AND DAY AND WE DON'T 

4344
03:51:55,560 --> 03:51:59,120
SEE THESE FLUCTUATIONS AN HENCE 

4345
03:51:59,120 --> 03:52:00,320
LOSE THIS IMPORTANT 

4346
03:52:00,320 --> 03:52:05,800
ENVIRONMENTAL CUE FOR PERIPHERAL

4347
03:52:05,800 --> 03:52:06,720
RHYTHM. 

4348
03:52:06,720 --> 03:52:10,080
WE CULTURED WITH THREE OTHER 

4349
03:52:10,080 --> 03:52:11,440
GROUPS WHO SIMILAR RESULTS 

4350
03:52:11,440 --> 03:52:13,760
WITHIN SIX MONTHS AN THIS IS ONE

4351
03:52:13,760 --> 03:52:15,280
OF THE MOST ROBUST RELATIONSHIPS

4352
03:52:15,280 --> 03:52:16,680
AND REPEATABLE RELATIONSHIPS TO 

4353
03:52:16,680 --> 03:52:20,800
BE FOUND IN A GUT MICROBIOME. 

4354
03:52:20,800 --> 03:52:22,920
YOU KNOW, WE TO THE THAT TO BE 

4355
03:52:22,920 --> 03:52:24,560
HONEST WE THOUGHT THAT WHEN WE 

4356
03:52:24,560 --> 03:52:25,840
PUBLISHED THAT WORK IT WOULD 

4357
03:52:25,840 --> 03:52:28,840
CHANGE THE WAY PEOPLE WOULD VIEW

4358
03:52:28,840 --> 03:52:29,760
MICROBIOME RESEARCH. 

4359
03:52:29,760 --> 03:52:31,480
MY COLLEAGUES IN THE OTHER LAB 

4360
03:52:31,480 --> 03:52:32,880
THAT PUBLISHED THIS BUT FIVE 

4361
03:52:32,880 --> 03:52:34,960
YEARS AFTER THE PUBLICATION OF 

4362
03:52:34,960 --> 03:52:40,200
THIS DATA, WE DID A QUICK SEARCH

4363
03:52:40,200 --> 03:52:42,840
FOR NATURE PUBLISHING GROUP 

4364
03:52:42,840 --> 03:52:45,160
SCIENCE PUBLISHING GROUPS CELL 

4365
03:52:45,160 --> 03:52:46,760
CRAFT AND ALL THE JOURNALS 

4366
03:52:46,760 --> 03:52:51,280
PUBLISHED BY ASM AND FOUND ABOUT

4367
03:52:51,280 --> 03:52:54,960
586 PUBLICATIONS IN THE YEAR 

4368
03:52:54,960 --> 03:52:58,400
2019 THAT PRESENTED NEW DATA, 

4369
03:52:58,400 --> 03:53:03,280
AND ONLY 5 REPORTED WHEN THEY 

4370
03:53:03,280 --> 03:53:04,520
RECORDED THEIR SAMPLES. 

4371
03:53:04,520 --> 03:53:06,360
33 HAD A RELATIVE REPORTING SUCH

4372
03:53:06,360 --> 03:53:08,200
AS THEY DID IT IN THE MORNING OR

4373
03:53:08,200 --> 03:53:09,840
BEFORE TREATMENT OR SOMETHING 

4374
03:53:09,840 --> 03:53:10,720
LIKE THAT. 

4375
03:53:10,720 --> 03:53:12,840
BUT THE VAST MAJORITY DO NOT 

4376
03:53:12,840 --> 03:53:15,160
PRESENT OR DO NOT DISCUSS WHEN, 

4377
03:53:15,160 --> 03:53:18,360
NOT EVEN LIKE HOW MANY WEEKS 

4378
03:53:18,360 --> 03:53:20,320
AFTER THEY STARTED THEIR 

4379
03:53:20,320 --> 03:53:21,600
INTERVENTION THAT THE MICROBIOME

4380
03:53:21,600 --> 03:53:24,560
WAS COLLECTED AND JUST TO GIVE 

4381
03:53:24,560 --> 03:53:27,440
YOU AN IDEA HERE, AS YOU CAN 

4382
03:53:27,440 --> 03:53:30,160
IMAGINE, WE LOOKED AT 

4383
03:53:30,160 --> 03:53:31,360
DISSIMILARITIES ACROSS TIME 

4384
03:53:31,360 --> 03:53:32,800
POINTS AND YOU CAN SEE THAT 

4385
03:53:32,800 --> 03:53:35,680
WITHIN A SPAN OF FOUR HOURS 

4386
03:53:35,680 --> 03:53:39,760
THERE IS A RADICAL CHANGE IN HOW

4387
03:53:39,760 --> 03:53:41,800
CLOSE OR SIMILAR THESE 

4388
03:53:41,800 --> 03:53:44,160
MICROBIOMES ARE TO EACH OTHER. 

4389
03:53:44,160 --> 03:53:46,280
SO IF SOME ONE WAS RECORDING, 

4390
03:53:46,280 --> 03:53:49,840
LET'S SAY YOU HAD A HOST WHO 

4391
03:53:49,840 --> 03:53:51,640
LIKED TO WORK LATE IN THE DAY 

4392
03:53:51,640 --> 03:53:52,840
THEY WOULD GET COMPLETELY 

4393
03:53:52,840 --> 03:53:55,360
DIFFERENT RESULTS IF THEY WENT 

4394
03:53:55,360 --> 03:53:58,560
TO THE MICE JUST BEFORE THE 

4395
03:53:58,560 --> 03:54:05,880
LIGHTS TURNED OFF IN YOUR MICE 

4396
03:54:05,880 --> 03:54:07,840
AQUARIUM YOU COULD PRACTICALLY 

4397
03:54:07,840 --> 03:54:11,240
SHOW ANY MICROBIOME RESULTS WANT

4398
03:54:11,240 --> 03:54:15,360
FROM YOUR STUDY SO THE TEMPLATE 

4399
03:54:15,360 --> 03:54:18,000
TIME IS VERY IMPORTANT IN THESE 

4400
03:54:18,000 --> 03:54:18,360
MEASURES. 

4401
03:54:18,360 --> 03:54:20,600
IN PARTICULAR WE WERE INTERESTED

4402
03:54:20,600 --> 03:54:23,360
IN A CONCEPT OF TIME RESTRICTED 

4403
03:54:23,360 --> 03:54:28,080
FEEDING, JUST TO REFRESH MEMORY,

4404
03:54:28,080 --> 03:54:34,360
MICE IN DIET INDUCED OBESITY 

4405
03:54:34,360 --> 03:54:38,560
LEADS TO LOW CYCLING OF 

4406
03:54:38,560 --> 03:54:40,160
METABOLIC RUMSFELD PER PHENOTYPE

4407
03:54:40,160 --> 03:54:41,560
BUT TIME RESTRICTED FEEDING 

4408
03:54:41,560 --> 03:54:43,920
WHERE WE RESTRICT ACCESS TO FOOD

4409
03:54:43,920 --> 03:54:45,960
TO ONLY THE NOCTURNAL PERIOD 

4410
03:54:45,960 --> 03:54:49,680
LEADS THESE MICE TO CONSUME THE 

4411
03:54:49,680 --> 03:54:51,200
SAME AM OF FOOD SO SAME NUMBER 

4412
03:54:51,200 --> 03:54:53,560
OF BLOCKS OF CHEESE BUT 

4413
03:54:53,560 --> 03:54:55,640
RESTRICTED TO THE NOCTURNAL 

4414
03:54:55,640 --> 03:54:59,320
PERIOD AND PRESERVE THESE HIGH 

4415
03:54:59,320 --> 03:55:01,680
AMPLITUDES FLUCTUATIONS AND 

4416
03:55:01,680 --> 03:55:04,000
PREVENT IN METABOLIC PHENOTYPE 

4417
03:55:04,000 --> 03:55:05,560
ASSOCIATED WITH HIGH FAT DIET. 

4418
03:55:05,560 --> 03:55:09,120
YOU KNOW WHEN WE DID MICROBIOME 

4419
03:55:09,120 --> 03:55:12,000
STUDYIES ON THESE GROUPS WE WERE

4420
03:55:12,000 --> 03:55:13,440
SURPRISED THERE WERE LITTLE 

4421
03:55:13,440 --> 03:55:16,480
DIFFERENCES THERE WAS 

4422
03:55:16,480 --> 03:55:19,480
RESTORATION OF THE CYCLICALNESS 

4423
03:55:19,480 --> 03:55:21,680
TO THE MICROBIOME BUT WE FOUND 

4424
03:55:21,680 --> 03:55:23,680
THAT EVEN THOUGH THE MIKE WOE 

4425
03:55:23,680 --> 03:55:24,760
BIOME DOESN'T SHIFT MUCH 

4426
03:55:24,760 --> 03:55:28,400
FUNCTIONALLY WE DO SEE A LOT OF 

4427
03:55:28,400 --> 03:55:32,760
SHIFT SO FOR EXAMPLE MY POST 

4428
03:55:32,760 --> 03:55:35,160
DOCTOR SHOWED THAT BIOACID IN 

4429
03:55:35,160 --> 03:55:53,520
THE ILIUM THERE'S A SWING FROM 

4430
03:55:53,520 --> 03:55:55,960
BIOACED DIFFERENCE THAT ARE 

4431
03:55:55,960 --> 03:55:58,120
RESTORED DEHIGH FAT DIET HAND 

4432
03:55:58,120 --> 03:56:00,760
THIS CORRESPONDED CHANGES IN 

4433
03:56:00,760 --> 03:56:03,280
BIOASIA I HAD SIGNALLING AS WELL

4434
03:56:03,280 --> 03:56:05,880
AS DOWNSTREAM TARGETS OF 

4435
03:56:05,880 --> 03:56:08,560
RECEPTORS AND ONE OF MY STUDENTS

4436
03:56:08,560 --> 03:56:12,320
IS WORKING ON THE TRANSCRIPT OF 

4437
03:56:12,320 --> 03:56:15,160
THESE MICE AND WHAT WE FOUND ONE

4438
03:56:15,160 --> 03:56:18,960
THING THAT WAS VERY DIFFERENT 

4439
03:56:18,960 --> 03:56:26,080
BETWEEN WAS THE CYCLICAL 

4440
03:56:26,080 --> 03:56:29,200
ACTIVITY, WHILE THE MOUSE EATS 

4441
03:56:29,200 --> 03:56:32,840
YOU SEE RESTRICTED MICE DON'T 

4442
03:56:32,840 --> 03:56:37,560
EXPRESS THE . . .  AND THE BACK 

4443
03:56:37,560 --> 03:56:41,960
PRACTICE ARE MORE EXPOSED TO 

4444
03:56:41,960 --> 03:56:45,800
BACK ARE THE A IN THE LUMEN THEY

4445
03:56:45,800 --> 03:56:48,960
START . . .  THIS GENE WE WERE 

4446
03:56:48,960 --> 03:56:52,240
THINK DOES BIOLACK PARTICULAR 

4447
03:56:52,240 --> 03:56:53,920
MODIFICATION AFFECT THE SIR KADE

4448
03:56:53,920 --> 03:56:56,600
YUN RHYTHM OF THE MOUSE OR THE 

4449
03:56:56,600 --> 03:56:56,920
METABOLISM. 

4450
03:56:56,920 --> 03:56:59,160
WE DECIDED TO TAKE A NEW 

4451
03:56:59,160 --> 03:57:01,320
APPROACH WHERE WE ISOLATED 

4452
03:57:01,320 --> 03:57:04,160
NEEDED BACTERIA, SPECIFICALLY IN

4453
03:57:04,160 --> 03:57:07,680
NATIVE E-COLI AND WE DECIDED TO 

4454
03:57:07,680 --> 03:57:08,960
ADD BENEFICIAL FUNCTIONS AND 

4455
03:57:08,960 --> 03:57:11,480
LABEL AND WHEN WE GAVE IT BACK 

4456
03:57:11,480 --> 03:57:13,640
TO THE MOUSE AND WE FOUND THAT 

4457
03:57:13,640 --> 03:57:15,960
BY DOING THIS WE CAN DO THESE 

4458
03:57:15,960 --> 03:57:20,040
KNOCK IN FUNCTION STUDIES AND 

4459
03:57:20,040 --> 03:57:23,560
FULLY CONVENTIONALIZE MICE 

4460
03:57:23,560 --> 03:57:25,280
WITHOUT ANTIBIOTICS BECAUSE 

4461
03:57:25,280 --> 03:57:25,960
ANTIBIOTICS AFFECT METABOLISM 

4462
03:57:25,960 --> 03:57:28,280
AND WE ARE ABLE TO ISOLATE THE 

4463
03:57:28,280 --> 03:57:31,440
FACT OF THE SINGLE FUNCTION. 

4464
03:57:31,440 --> 03:57:33,360
WHAT WE SAW WITH ENGINEERED NATE

4465
03:57:33,360 --> 03:57:37,320
I HAVE BACTERIA IS THAT ONE OF 

4466
03:57:37,320 --> 03:57:39,000
THINGS CAUSED BY COVID WAS IT 

4467
03:57:39,000 --> 03:57:40,800
HELPED EXTEND THE STUDY FOR MORE

4468
03:57:40,800 --> 03:57:43,400
THAN TWO YEARS WHERE WE HAD 

4469
03:57:43,400 --> 03:57:49,560
FOUND OUT NOT ONLY PERSISTENT 

4470
03:57:49,560 --> 03:57:51,160
COLONIZATION BUT WE FOUND THE 

4471
03:57:51,160 --> 03:57:52,360
BACTERIA MAINTAINS ITS FUNCTION 

4472
03:57:52,360 --> 03:57:58,800
BETWEEN TWO YEARS OF THE STUDY. 

4473
03:57:58,800 --> 03:58:02,120
>> YOU HAVE ABOUT TWO AND A HALF

4474
03:58:02,120 --> 03:58:02,360
MINUTES. 

4475
03:58:02,360 --> 03:58:03,680
>> OKAY. 

4476
03:58:03,680 --> 03:58:06,840
CAUSE OF WEIGHT LOSS AN IMPROVE 

4477
03:58:06,840 --> 03:58:09,880
INSULIN SENSITIVITY BUT WE 

4478
03:58:09,880 --> 03:58:11,120
DIDN'T NOTICE ANY WEIGHT WITH 

4479
03:58:11,120 --> 03:58:15,520
OUR FULLY CONVENTIONALIZED MICE 

4480
03:58:15,520 --> 03:58:18,560
BUT WE NOTICED A DIFFERENCE IN 

4481
03:58:18,560 --> 03:58:20,480
MIXED MEAL GLUCOSE AN INSULIN 

4482
03:58:20,480 --> 03:58:24,600
AND DID REVERSE THE PHENOTYPE IN

4483
03:58:24,600 --> 03:58:27,160
AN OBOB MOUSE THAT WAS ABLE TO 

4484
03:58:27,160 --> 03:58:30,360
IMPROVE SENSITIVITY BUT IT 

4485
03:58:30,360 --> 03:58:32,200
AFFECTS CIRCADIAN RHYTHM SO WE 

4486
03:58:32,200 --> 03:58:33,920
DECIDED TO PURSUE THIS IN 

4487
03:58:33,920 --> 03:58:36,200
ANOTHER MODEL. 

4488
03:58:36,200 --> 03:58:41,280
THIS IS AN H MOUSE WHERE WE 

4489
03:58:41,280 --> 03:58:44,000
NOTICED THAT H MICE WEIGH MORE 

4490
03:58:44,000 --> 03:58:45,440
EVER BODY FAT EVER INSULIN 

4491
03:58:45,440 --> 03:58:47,840
RESISTANCE AND EVER THAT DESPITE

4492
03:58:47,840 --> 03:58:49,960
CONSUMING LESS FOOD AND DO 

4493
03:58:49,960 --> 03:58:55,400
SPREAD THEIR CALORIE INTAKE. 

4494
03:58:55,400 --> 03:59:01,760
ONE OF MY POST DOCS FOUND 

4495
03:59:01,760 --> 03:59:04,040
THAT . . .  WAS DIFFERENT 

4496
03:59:04,040 --> 03:59:05,800
BETWEEN YOUNG AGE MICE SO WE 

4497
03:59:05,800 --> 03:59:09,080
DECIDED TO USE BACTERIA TO SEE 

4498
03:59:09,080 --> 03:59:10,440
HOW IT AFFECTS THIS AGE 

4499
03:59:10,440 --> 03:59:13,480
ASSOCIATED PHENOTYPE AND HE 

4500
03:59:13,480 --> 03:59:20,920
FOUND THE . . .  DID IMPROVE 

4501
03:59:20,920 --> 03:59:23,040
APPROVE INSULIN SENSITIVITY BUT 

4502
03:59:23,040 --> 03:59:25,560
IT RESTORED EATING PATTERNS AND 

4503
03:59:25,560 --> 03:59:28,080
OTHER CIRCADIAN ASPECTS OF THE 

4504
03:59:28,080 --> 03:59:30,800
MOUSE THAT WE HAD MEASURED. 

4505
03:59:30,800 --> 03:59:37,960
SO OVERALL THE LUM INAL 

4506
03:59:37,960 --> 03:59:39,320
ENVIRONMENT, WHAT DOES IT MEAN 

4507
03:59:39,320 --> 03:59:41,280
TO SAY THE MICROBIOME IS 

4508
03:59:41,280 --> 03:59:42,920
DIFFERENT BETWEEN EXPERIMENT AND

4509
03:59:42,920 --> 03:59:43,720
CONTROL WHEN THE DIFFERENCE 

4510
03:59:43,720 --> 03:59:48,480
BETWEEN NIGHT AND DAY IS FAR 

4511
03:59:48,480 --> 03:59:49,640
DIFFERENT? 

4512
03:59:49,640 --> 03:59:52,480
SO, REALLY, THE IMPORTANCE OF 

4513
03:59:52,480 --> 03:59:55,760
THIS DYNAMIC OF THE MICROBIOME 

4514
03:59:55,760 --> 04:00:00,320
NEED TO BE FURTHER EXPLORED. 

4515
04:00:00,320 --> 04:00:05,320
LACK OF ACCOUNTING TIME, LUM 

4516
04:00:05,320 --> 04:00:11,320
INAL FLUKSZ ARE IMPORTANT AND 

4517
04:00:11,320 --> 04:00:18,760
BEING INVESTIGATED BY LOTS OF 

4518
04:00:18,760 --> 04:00:19,640
PEOPLE INCLUDING US. 

4519
04:00:19,640 --> 04:00:21,560
SCIENCE IS NOT DONE IN 

4520
04:00:21,560 --> 04:00:21,960
ISOLATION. 

4521
04:00:21,960 --> 04:00:23,840
WE CERTAINLY COULD NOT HAVE DONE

4522
04:00:23,840 --> 04:00:25,000
ALL THIS WORK WITHOUT THE 

4523
04:00:25,000 --> 04:00:26,640
SUPPORT OF OUR COLLABORATEDERS 

4524
04:00:26,640 --> 04:00:29,800
AND OUR FUNDERS, PRIMARILY NIH 

4525
04:00:29,800 --> 04:00:32,960
SO THANK YOU SO MUCH FOR THIS 

4526
04:00:32,960 --> 04:00:33,280
OPPORTUNITY. 

4527
04:00:33,280 --> 04:00:35,360
>> THANK YOU VERY MUCH FOR THAT 

4528
04:00:35,360 --> 04:00:37,560
ASSIMILATING TALK ON THE 

4529
04:00:37,560 --> 04:00:39,160
CIRCADIAN RHYTHM AND ITS IMPACT 

4530
04:00:39,160 --> 04:00:40,960
ON THE MICROBIOME. 

4531
04:00:40,960 --> 04:00:42,840
KATHERINE I'LL TURN IT OVER TO 

4532
04:00:42,840 --> 04:00:43,040
YOU. 

4533
04:00:43,040 --> 04:00:46,840
>> WELL, THANK YOU DR. HAMILTON.

4534
04:00:46,840 --> 04:00:49,760
WE ARE ACTUALLY MOVING NOW TO A 

4535
04:00:49,760 --> 04:00:50,000
BREAK. 

4536
04:00:50,000 --> 04:00:51,160
WE HAVE A BRIEF BREAK HERE. 

4537
04:00:51,160 --> 04:00:54,040
WE ARE GOING TO BE COMING BACK I

4538
04:00:54,040 --> 04:00:57,560
BELIEVE AT 3:30 P.M. SHARP AND I

4539
04:00:57,560 --> 04:01:00,200
WANT TO THANK THE PRESENTERS WHO

4540
04:01:00,200 --> 04:01:00,880
SPOKE. 

4541
04:01:00,880 --> 04:01:02,680
I'M LOOKING FORWARD TO HEARING 

4542
04:01:02,680 --> 04:01:04,760
FROM THE REST OF THE SPEAKERS IN

4543
04:01:04,760 --> 04:01:06,760
SESSION TWO WHEN WE RETURN 

4544
04:01:06,760 --> 04:01:23,160
PROMPTLY AT 3:30. 

4545
04:01:23,160 --> 04:01:24,960
>> DR HAMILTON BACK TO YOU

4546
04:01:24,960 --> 04:01:28,400
>> THANK YOU MANY IT IS GIVES ME

4547
04:01:28,400 --> 04:01:34,480
GREAT PLEASURE TO WELCOME 

4548
04:01:34,480 --> 04:01:49,320
DR. SHARON. 

4549
04:01:49,320 --> 04:01:50,920
>> SO THANK YOU VERY MUCH FOR 

4550
04:01:50,920 --> 04:01:54,720
THE INVITATION TO PRESENT AN I'M

4551
04:01:54,720 --> 04:01:57,400
VERY EXCITED TO SHARE SOME OF 

4552
04:01:57,400 --> 04:01:58,680
OUR RESEARCH. 

4553
04:01:58,680 --> 04:02:01,360
SO, I OFTENTIMES TALK ABOUT 

4554
04:02:01,360 --> 04:02:04,120
RESEARCH LOOKING AT INTO A BLACK

4555
04:02:04,120 --> 04:02:04,320
BOX. 

4556
04:02:04,320 --> 04:02:08,520
MY LAB CONDUCTS BASICS AN 

4557
04:02:08,520 --> 04:02:10,280
TRANSLATIONAL RESEARCH FOCUSED 

4558
04:02:10,280 --> 04:02:12,560
ON DIETARY COMPONENTS 

4559
04:02:12,560 --> 04:02:13,920
PARTICULARLY HUMAN MILK 

4560
04:02:13,920 --> 04:02:14,240
COMPONENTS. 

4561
04:02:14,240 --> 04:02:22,200
WE HEARD A LOT ABOUT THE HUMAN 

4562
04:02:22,200 --> 04:02:27,800
GLUK OH SOOK RIDES. 

4563
04:02:27,800 --> 04:02:30,720
WE CAN FAIRLY EASILY GET STOOL 

4564
04:02:30,720 --> 04:02:33,600
SAMPLES TO MEASURE METABOLITES 

4565
04:02:33,600 --> 04:02:37,120
BUT WHAT HAS BEEN TRICKY IS 

4566
04:02:37,120 --> 04:02:41,160
GETTING ACCESS TO HOST GENOME 

4567
04:02:41,160 --> 04:02:42,880
AND EPI GENOME. 

4568
04:02:42,880 --> 04:02:45,960
SO A NUMBER OF YEARS AGO I 

4569
04:02:45,960 --> 04:02:47,800
APPROACHED A COLLEAGUE TWO GOOD 

4570
04:02:47,800 --> 04:02:51,960
COLLEAGUES ABOUT A NON-INVASIVE 

4571
04:02:51,960 --> 04:02:56,760
APPROACH SO DR. RAP CHAP KIN AND

4572
04:02:56,760 --> 04:02:58,200
LAURIE AT TEXAS A & M HAD 

4573
04:02:58,200 --> 04:03:04,120
DEVELOPED A WAY TO EXFOLIATE A 

4574
04:03:04,120 --> 04:03:06,760
CELL TRANSCRIPTO. 

4575
04:03:06,760 --> 04:03:10,920
WE HAVE BEEN LIMITED BY LACK OF 

4576
04:03:10,920 --> 04:03:14,600
INVASIVE WAY TO BUT WE LEARNED 

4577
04:03:14,600 --> 04:03:18,360
THAT A 6TH OF EPITHELIAL CELLS 

4578
04:03:18,360 --> 04:03:23,440
ARE SHEDDED THROUGH GUT 

4579
04:03:23,440 --> 04:03:25,000
TURNOVER . . .  AND OTHERS HAVE 

4580
04:03:25,000 --> 04:03:27,480
SHOWN THAT THESE CELLS ARE MADE 

4581
04:03:27,480 --> 04:03:29,240
VIABILITY CONNECTS TO CULTURED 

4582
04:03:29,240 --> 04:03:31,760
AND YOU CAN MEASURE NUTRIENTS IN

4583
04:03:31,760 --> 04:03:32,840
THEM AS WELL. 

4584
04:03:32,840 --> 04:03:38,360
SO DR. CHAP KINS FOCUS WAS ON I 

4585
04:03:38,360 --> 04:03:40,280
SAID YOU THINK THIS CAN BE 

4586
04:03:40,280 --> 04:03:43,080
APPLIED TO HUMAN INFANTS. 

4587
04:03:43,080 --> 04:03:46,760
SO WE CONDUCTED A PROOF OF 

4588
04:03:46,760 --> 04:03:55,000
CONCEPT STUDY WHERE WE COLLECTED

4589
04:03:55,000 --> 04:03:59,600
STOOL SAMPLES OF VAGINAL 

4590
04:03:59,600 --> 04:04:01,960
DELIVERED MOTHERS AND ALL 

4591
04:04:01,960 --> 04:04:03,920
INFANTS WERE FED THE SAME 

4592
04:04:03,920 --> 04:04:06,040
FORMULA AS WELL. 

4593
04:04:06,040 --> 04:04:08,880
SO, THE TECHNIQUE BASICALLY 

4594
04:04:08,880 --> 04:04:10,480
STOOL SAMPLES ARE COLLECTED FROM

4595
04:04:10,480 --> 04:04:13,000
THE DIAPER PUT IMMEDIATELY INTO 

4596
04:04:13,000 --> 04:04:16,920
A DENATUREATION SOLUTION AND 

4597
04:04:16,920 --> 04:04:19,280
THEN THESE THIS MIXED BY HAND SO

4598
04:04:19,280 --> 04:04:20,880
THIS IS ACTUALLY DONE IN THE 

4599
04:04:20,880 --> 04:04:21,480
HOME. 

4600
04:04:21,480 --> 04:04:24,720
THE MOTHER OF THIS INFANT WHO IS

4601
04:04:24,720 --> 04:04:27,080
DOING THE SIMPLE COLLECTION AND 

4602
04:04:27,080 --> 04:04:28,640
THEN, THE SAMPLES WERE TAKEN 

4603
04:04:28,640 --> 04:04:31,840
INTO THE LAB AND AT THIS TIME WE

4604
04:04:31,840 --> 04:04:35,840
WERE DOING GENE MARKER AWAY, WE 

4605
04:04:35,840 --> 04:04:38,320
ARE NOW DOING SEQUENCING BUT 

4606
04:04:38,320 --> 04:04:41,600
DR. CHAP KIN HAS DEVELOPED A 

4607
04:04:41,600 --> 04:04:46,400
TECHNIQUE TO ENENRICH THE 

4608
04:04:46,400 --> 04:04:49,200
MAMMALIAN MRNA . . .  SO IT 

4609
04:04:49,200 --> 04:04:52,400
WORKED WELL, NOW WITH SEQUENCING

4610
04:04:52,400 --> 04:04:55,880
THERE'S A LOT OF MAY BE ROBAL 

4611
04:04:55,880 --> 04:04:57,120
SIGNATURES IN THERE BUT ARE 

4612
04:04:57,120 --> 04:04:59,280
SOMEWHAT ABLE TO ENRICH THE HOST

4613
04:04:59,280 --> 04:05:01,440
SO WE STARTED WITH 57,000 GENES.

4614
04:05:01,440 --> 04:05:04,800
AGAIN WE WERE TRYING TO BE 

4615
04:05:04,800 --> 04:05:05,800
CONSERVATIVE BECAUSE OF SOME OF 

4616
04:05:05,800 --> 04:05:08,000
THE ISSUES THAT WERE RAISED THIS

4617
04:05:08,000 --> 04:05:11,840
MORNING ABOUT MULTI-OMICS AND 

4618
04:05:11,840 --> 04:05:15,600
FALSE DISCOVERY SO WE SELECTED 

4619
04:05:15,600 --> 04:05:18,160
4200 GENES ON ALL THE ARRAYS SO 

4620
04:05:18,160 --> 04:05:22,920
IF IT WAX ONLY IN THE BREASTFED 

4621
04:05:22,920 --> 04:05:25,720
INFANT SIMPLE OR FORMULA FED IT 

4622
04:05:25,720 --> 04:05:26,920
WASN'T INCLUDED. 

4623
04:05:26,920 --> 04:05:28,840
AFTER THE CORRECTIONS FOR FALSE 

4624
04:05:28,840 --> 04:05:30,440
DISCOVERY RATES WE FOUND ABOUT 

4625
04:05:30,440 --> 04:05:33,640
1200 YEENS THAT WERE 

4626
04:05:33,640 --> 04:05:35,040
SIGNIFICANTLY DIFFERENT AND FEW 

4627
04:05:35,040 --> 04:05:36,280
L'S THAN .05. 

4628
04:05:36,280 --> 04:05:38,600
AGAIN TO REDUCE THE POTENTIAL 

4629
04:05:38,600 --> 04:05:43,040
FOR FALSE DISCOVERY WE HAD A 

4630
04:05:43,040 --> 04:05:45,360
PRIORI DEVELOPED A LIST OF GENES

4631
04:05:45,360 --> 04:05:47,640
WE HIGH HYPOTHESIZEth MIGHT BY 

4632
04:05:47,640 --> 04:05:49,280
DIFFERENT IN THE GUT VSZ FORMULA

4633
04:05:49,280 --> 04:05:52,880
OR BREASTFED INFANTS LISTED 529 

4634
04:05:52,880 --> 04:05:53,240
YEARS. 

4635
04:05:53,240 --> 04:05:56,600
WE WEATHER I HADDED THE 1200 

4636
04:05:56,600 --> 04:05:58,720
GENES ON THAT AND ENDED UP WITH 

4637
04:05:58,720 --> 04:05:59,320
146 GENES. 

4638
04:05:59,320 --> 04:06:02,640
THOSE WERE SUBJECTED TO A NUMBER

4639
04:06:02,640 --> 04:06:06,600
OF STATISTICAL AND . . .  

4640
04:06:06,600 --> 04:06:11,400
ANALYSES ONE BEING LINEAR 

4641
04:06:11,400 --> 04:06:13,840
DISCRIMINATE ANALYSIS TO DECIDE 

4642
04:06:13,840 --> 04:06:17,440
WHICH GENES PROVIDE THE BEST 

4643
04:06:17,440 --> 04:06:19,640
CLASSIFIES OF BREAST vs. FORMULA

4644
04:06:19,640 --> 04:06:22,240
FED INFANTS AND UPLOADED TO 

4645
04:06:22,240 --> 04:06:28,000
UNDERSTAND THEIR NETWORKS AND 

4646
04:06:28,000 --> 04:06:28,640
RELATIONSHIPS. 

4647
04:06:28,640 --> 04:06:32,360
WE LOOK AT ONE AND TWO AND THREE

4648
04:06:32,360 --> 04:06:33,440
GENE COMBINATIONS AND SEEING 

4649
04:06:33,440 --> 04:06:34,640
SEPARATION OF OUR GROUPS. 

4650
04:06:34,640 --> 04:06:36,840
ONE THING I NOTICED THE 

4651
04:06:36,840 --> 04:06:38,160
BREASTFED WE SEE MORE 

4652
04:06:38,160 --> 04:06:39,640
VARIABILITY THAN WITH THE 

4653
04:06:39,640 --> 04:06:41,240
FORMULA FED INFANTS AND JUST TO 

4654
04:06:41,240 --> 04:06:46,640
GIVE SOME IDEAS OF THE GENES, 

4655
04:06:46,640 --> 04:06:51,040
E-PASS ONE WHICH IS H I FM 1 

4656
04:06:51,040 --> 04:06:53,440
ALPHA WAS THE MOST 

4657
04:06:53,440 --> 04:06:55,240
DISCRIMINATORY GENE BETWEEN 

4658
04:06:55,240 --> 04:07:02,160
FORMULA AND BREASTFED INFANTS. 

4659
04:07:02,160 --> 04:07:04,160
LDA DOES DEPENDENT ON WHOLE 

4660
04:07:04,160 --> 04:07:06,040
CHANGES BUT WE ALSO WERE 

4661
04:07:06,040 --> 04:07:07,120
INTERESTED IN WHOLE CHANGE 

4662
04:07:07,120 --> 04:07:08,400
DIFFERENCES SO IT'S IMPORTANT TO

4663
04:07:08,400 --> 04:07:11,960
NOTE THAT THE GENES THAT ARE 

4664
04:07:11,960 --> 04:07:19,640
MOST DISCRIMINATORY WERE ALL 

4665
04:07:19,640 --> 04:07:21,400
UPGRADED IN BREASTFED AND WE 

4666
04:07:21,400 --> 04:07:23,600
HAVE SEEN THAT THE GET EFFECT 

4667
04:07:23,600 --> 04:07:28,960
SEEMS TO BE DOWN REGULATING GENE

4668
04:07:28,960 --> 04:07:29,240
EXPRESSION. 

4669
04:07:29,240 --> 04:07:31,360
WE WERE SEEING A LOT OF 

4670
04:07:31,360 --> 04:07:34,440
TRANSCRIPTION FACTORS BUT SEEING

4671
04:07:34,440 --> 04:07:37,360
A NUMBER OF IMPORTANT GENES I 

4672
04:07:37,360 --> 04:07:39,840
SAID ONE ALPHA, IT'S TWO ALPHA, 

4673
04:07:39,840 --> 04:07:41,320
AND I WORK AND CONTINUE TO WORK 

4674
04:07:41,320 --> 04:07:43,360
WITH PRE-TERM INFANTS SO WHAT'S 

4675
04:07:43,360 --> 04:07:45,720
INTERESTING IS WE KNOW THAT 

4676
04:07:45,720 --> 04:07:51,640
BREASTFEEDING PROTECTS AGAINST A

4677
04:07:51,640 --> 04:07:54,480
DISEASE CALLED . . .  AND WE 

4678
04:07:54,480 --> 04:07:56,600
DON'T EVER AUNTHING OF THE MEDIC

4679
04:07:56,600 --> 04:07:59,120
NICHES BUT WE FOUND IN TERM 

4680
04:07:59,120 --> 04:08:02,360
INFANTS WE FOUND THE MOST 

4681
04:08:02,360 --> 04:08:05,720
CRIMINAL STORY TRANSCRIPT OME 

4682
04:08:05,720 --> 04:08:08,040
LETS THE GENE CELLS BE MORE 

4683
04:08:08,040 --> 04:08:09,960
TOLERANT TO HYPOXIA SO THAT IS 

4684
04:08:09,960 --> 04:08:11,920
SOMETHING WE ARE FOLLOWING UP TO

4685
04:08:11,920 --> 04:08:13,560
SEE IF THAT PROTECTIVE EFFECT IS

4686
04:08:13,560 --> 04:08:14,920
PROTECTING THOSE CELLS FROM 

4687
04:08:14,920 --> 04:08:17,560
GOING INTO NECROSIS. 

4688
04:08:17,560 --> 04:08:20,640
THROUGH META CORPS WE WERE ABLE 

4689
04:08:20,640 --> 04:08:26,240
TO SEE THE MAJOR GENE NETWORKS 

4690
04:08:26,240 --> 04:08:28,600
AND PATH WAYS AND THEY WERE 

4691
04:08:28,600 --> 04:08:30,280
HIGHLY SIGNIFICANT AN ALL THESE 

4692
04:08:30,280 --> 04:08:32,560
REALLY SUPPORT THE SORT OF 

4693
04:08:32,560 --> 04:08:34,040
CLINICAL EM DEEM LOGICAL 

4694
04:08:34,040 --> 04:08:35,120
DIFFERENCES THAT WE'VE SEEN 

4695
04:08:35,120 --> 04:08:36,640
BETWEEN BREASTFED AND FORMULA 

4696
04:08:36,640 --> 04:08:38,280
FED INFANTS BUT I'LL HAVE TO 

4697
04:08:38,280 --> 04:08:42,360
TELL YOU AT THIS, WHEN WE GOT 

4698
04:08:42,360 --> 04:08:46,120
THIS DATA, I HAD BEEN STUDYING 

4699
04:08:46,120 --> 04:08:48,040
BRESD AND FORMULA FEEDING 20 

4700
04:08:48,040 --> 04:08:51,240
YEARS AND WAS SURPRISED WE ARE 

4701
04:08:51,240 --> 04:08:52,160
CHANGING FUNDAMENTAL GENES 

4702
04:08:52,160 --> 04:08:55,560
INVOLVED IN GUT DEVELOPMENT, YOU

4703
04:08:55,560 --> 04:09:01,640
KNOW, GUT PROLIFERATION AN NOTCH

4704
04:09:01,640 --> 04:09:02,440
DIFFERENTIATION SO THIS PROVIDE 

4705
04:09:02,440 --> 04:09:04,840
US AN INSIDE INTO THIS BLACK BOX

4706
04:09:04,840 --> 04:09:07,440
IN TERMS OF WHAT IS THE 

4707
04:09:07,440 --> 04:09:08,560
RELATIONSHIP BETWEEN DIET 

4708
04:09:08,560 --> 04:09:10,720
POST-GENE EXPRESSION AND WE CAN 

4709
04:09:10,720 --> 04:09:12,720
USE THESE GENE COMBINATIONS AND 

4710
04:09:12,720 --> 04:09:15,960
BIOMARKERS TO DIMINNISH AND SO, 

4711
04:09:15,960 --> 04:09:24,400
IT HELPS O' -- TO GIVE FORMULA 

4712
04:09:24,400 --> 04:09:24,760
COMPOSITION. 

4713
04:09:24,760 --> 04:09:27,520
WE DID A COMPARISON OF PRE-TERM 

4714
04:09:27,520 --> 04:09:30,200
vs. TERM INFANTS AND IN THIS 

4715
04:09:30,200 --> 04:09:34,000
CASE ABLE TO SHOW THE 

4716
04:09:34,000 --> 04:09:42,280
DEVELOPMENTAL DIFFERENCE HIGHER 

4717
04:09:42,280 --> 04:09:46,480
INFLAMMATORY GENE EXPRESSION AND

4718
04:09:46,480 --> 04:09:52,040
AN NIH GRANT SO WHEN WE SUBMIT 

4719
04:09:52,040 --> 04:09:53,560
THESE PAPERS THE ONE QUESTION 

4720
04:09:53,560 --> 04:09:55,360
ALWAYS COMES LIKE WHERE ARE 

4721
04:09:55,360 --> 04:09:58,200
THREE CELLS COMING FROM AND WE 

4722
04:09:58,200 --> 04:10:01,840
KNEW WE COULD SEE SMALL 

4723
04:10:01,840 --> 04:10:03,240
INTESTINAL SIGNATURES BUT WHAT 

4724
04:10:03,240 --> 04:10:05,840
WE DID WAS WENT BACK STARTED THE

4725
04:10:05,840 --> 04:10:07,680
REVERSE TRANSLATION, TALKING 

4726
04:10:07,680 --> 04:10:09,800
ABOUT INTO THE PIGLET MODEL SO 

4727
04:10:09,800 --> 04:10:11,760
THIS IS A GRAPHICAL ABSTRACT SO 

4728
04:10:11,760 --> 04:10:14,920
WHAT WE ACTUALLY COLLECTED WERE 

4729
04:10:14,920 --> 04:10:19,360
MUCOSAL SAMPLES FROM THE ILIUM A

4730
04:10:19,360 --> 04:10:22,440
SENDING AND DESCENDING COLON AND

4731
04:10:22,440 --> 04:10:25,520
LUM NATURAL CONTENTS FROM SAY 

4732
04:10:25,520 --> 04:10:29,080
SENDING AND DESCENDING COLON SO 

4733
04:10:29,080 --> 04:10:32,040
YOU SEE A VERY RIGHT OF CELL 

4734
04:10:32,040 --> 04:10:35,520
TYPES AN LOOKED AT THE 

4735
04:10:35,520 --> 04:10:39,760
TRANSCRIPTOME AND IF YOU LOOK AT

4736
04:10:39,760 --> 04:10:44,040
ILIUM A.C. AND D.C. MUCOSA WE 

4737
04:10:44,040 --> 04:10:47,520
FOUND ABOUT 12,000 GOALS AND IN 

4738
04:10:47,520 --> 04:10:55,040
THE EX-FOLIOME THERE DESCENDING 

4739
04:10:55,040 --> 04:10:58,760
COLON EX-FOLIOME IS THE FOLD 

4740
04:10:58,760 --> 04:11:01,280
ABOVE THE RECTUM SO WE COLLECT 

4741
04:11:01,280 --> 04:11:02,440
THIS BECAUSE IT HASN'T BEEN SHED

4742
04:11:02,440 --> 04:11:04,440
AND YOU DON'T KNOW HOW LONG IT'S

4743
04:11:04,440 --> 04:11:07,920
BEEN OUT SO THIS WAY IT'S READY 

4744
04:11:07,920 --> 04:11:10,120
TO BE VOIDED FECAL SIMPLE SO WE 

4745
04:11:10,120 --> 04:11:11,600
THINK THIS IS CLOSE TO WHAT WE 

4746
04:11:11,600 --> 04:11:13,240
ARE SEEING IN OUR HUMAN INFANTS 

4747
04:11:13,240 --> 04:11:16,240
IN THE THIS CASE WE ARE SEEING 

4748
04:11:16,240 --> 04:11:20,840
ABOUT 6,000 GENES AND 50 PERCENT

4749
04:11:20,840 --> 04:11:22,960
OVERLAP WITH THE GENES. 

4750
04:11:22,960 --> 04:11:25,000
AND ABOUT 94 PERCENT OVERLAP 

4751
04:11:25,000 --> 04:11:29,880
BETWEEN THE GENES AND THE A.C. 

4752
04:11:29,880 --> 04:11:33,200
EX-FOLIOME SO JUST PAST THE I 

4753
04:11:33,200 --> 04:11:36,400
WILL YAL JUNCTION AN D.C. SO 

4754
04:11:36,400 --> 04:11:38,360
SEEMS ONCE THOSE CELLS GET 

4755
04:11:38,360 --> 04:11:39,880
EX-POLL YAITD THEY'RE FAIRLY 

4756
04:11:39,880 --> 04:11:41,840
STABLE. 

4757
04:11:41,840 --> 04:11:47,280
SO WE THEN WENT AND WE HAD 

4758
04:11:47,280 --> 04:11:49,040
GENERATED LISTS OF DIFFERENT 

4759
04:11:49,040 --> 04:11:50,040
GENES REPRESENTATIVE OF 

4760
04:11:50,040 --> 04:11:51,440
DIFFERENT REGIONS IN THE GUT SO 

4761
04:11:51,440 --> 04:11:54,320
TO ORIENT YOU FOR THE NEXT FEW 

4762
04:11:54,320 --> 04:11:57,200
SLIDES, YOU SEE ILIUM MUCOSA, 

4763
04:11:57,200 --> 04:11:59,640
A.C. NEW COAST, A D.C. MUCOSA 

4764
04:11:59,640 --> 04:12:03,360
AND THEN THE A.C. AND D.C. 

4765
04:12:03,360 --> 04:12:05,640
EX-POLL GOME SO THE DARKER BLUE 

4766
04:12:05,640 --> 04:12:06,720
SHOWS THE GENES. 

4767
04:12:06,720 --> 04:12:08,280
SO IT'S CLEAR WE ARE SEEING IN 

4768
04:12:08,280 --> 04:12:12,280
THE A.C. AND D.C. EX-FOLIOME 

4769
04:12:12,280 --> 04:12:14,360
GENES THAT ARE EXPRESSED IN THE 

4770
04:12:14,360 --> 04:12:19,880
ILIUM BUT TO LESSER DEGREE IN 

4771
04:12:19,880 --> 04:12:22,040
THE COLON SO IT'S JUST 

4772
04:12:22,040 --> 04:12:23,640
REPRESENTING THE MUCOSAL 

4773
04:12:23,640 --> 04:12:24,680
UNDERLYING IT. 

4774
04:12:24,680 --> 04:12:27,760
SO THESE WERE DIFFERENT AREAS OF

4775
04:12:27,760 --> 04:12:28,920
THE GUT. 

4776
04:12:28,920 --> 04:12:30,840
THESE WERE AGAIN GENE MARKERS 

4777
04:12:30,840 --> 04:12:33,840
FOR VARIOUS CELL TYPES SO YOU 

4778
04:12:33,840 --> 04:12:37,680
COULD SEE STEM-CELLS, TRANSIT 

4779
04:12:37,680 --> 04:12:40,400
AMPLIFYING CELLS AND YOU KNOW, 

4780
04:12:40,400 --> 04:12:44,640
VERY GOOD SIGNATURES AND THEN, 

4781
04:12:44,640 --> 04:12:48,760
LASTLY, WE COMPARED SO DONE A 

4782
04:12:48,760 --> 04:12:51,240
NICE PAPER ON HUMAN INTESTINE 

4783
04:12:51,240 --> 04:12:56,160
AND SO WE MAPPED OUR PIGLET 

4784
04:12:56,160 --> 04:12:59,600
EX-FOL

4785
04:12:59,600 --> 04:13:01,920
EX-FOLIOME AND MUCOSAL CELLS ON 

4786
04:13:01,920 --> 04:13:03,080
THIS. 

4787
04:13:03,080 --> 04:13:08,400
SO LOOKING AT THIS AS FINDING 

4788
04:13:08,400 --> 04:13:11,160
GENES IF YOU GO ACROSS THE 

4789
04:13:11,160 --> 04:13:15,200
BOTTOM IN LIPID BIOSALT VITAMIN,

4790
04:13:15,200 --> 04:13:17,840
ALSO TRANSPORTER GENES AS WELL 

4791
04:13:17,840 --> 04:13:20,040
AS HORMONES AND IMMUNE GENES AND

4792
04:13:20,040 --> 04:13:22,440
I THINK ONE THINGS REALLY 

4793
04:13:22,440 --> 04:13:26,240
EXCITING TO US IF WE BLOW THIS 

4794
04:13:26,240 --> 04:13:29,840
UP YOU'LL SEE THAT FOR SEVERAL 

4795
04:13:29,840 --> 04:13:33,680
GENES PARTICULARLY FATTY ACED 

4796
04:13:33,680 --> 04:13:38,480
BINDING 2 USED AS ANOTHER 

4797
04:13:38,480 --> 04:13:43,120
SUPPORTER AND STRONG EXPRESSION 

4798
04:13:43,120 --> 04:13:45,600
IN THE GRANT THAT WE'VE 

4799
04:13:45,600 --> 04:13:46,880
SUBMITTED IS BASICALLY TO MAKE 

4800
04:13:46,880 --> 04:13:49,040
THE POINT THAT WE THINK THAT WE 

4801
04:13:49,040 --> 04:13:53,960
CAN USE THIS EX-FOLIOME TO GAIN 

4802
04:13:53,960 --> 04:13:56,080
INSIGHT INTO SMALL INTESTINAL 

4803
04:13:56,080 --> 04:13:57,160
FUNCTIONAL GENES. 

4804
04:13:57,160 --> 04:13:59,320
>> YOU HAVE THREE MINUTES. 

4805
04:13:59,320 --> 04:14:05,320
>> SO, I THINK PERTINENT TO THIS

4806
04:14:05,320 --> 04:14:07,440
WORKSHOP IS REALLY THEN CAN WE 

4807
04:14:07,440 --> 04:14:10,440
USE THIS ALSO TO LOOK AT HOST 

4808
04:14:10,440 --> 04:14:12,400
MICROBE INTERACTIONS. 

4809
04:14:12,400 --> 04:14:15,520
SO USING THE ORIGINAL CHAP KIN 

4810
04:14:15,520 --> 04:14:18,840
STUD WE'VE THE HOST GENE 

4811
04:14:18,840 --> 04:14:21,920
EXPRESSION AND THEN WITHIN THE 

4812
04:14:21,920 --> 04:14:24,880
SAME STOOL SAMPLES WE SEQUENCE 

4813
04:14:24,880 --> 04:14:28,360
THE 16-A AND META GENOME AND YOU

4814
04:14:28,360 --> 04:14:30,360
CAN SEE THIS IS THE FINAL LEVEL 

4815
04:14:30,360 --> 04:14:32,520
BETWEEN FORMULA AND BREASTFED 

4816
04:14:32,520 --> 04:14:33,360
INFANTS. 

4817
04:14:33,360 --> 04:14:36,680
YOU CAN SEE QUITE SIGNIFICANT 

4818
04:14:36,680 --> 04:14:40,640
DIFFERENCES, HIGH LEVELS OF BACK

4819
04:14:40,640 --> 04:14:45,480
TROIDZ AND PROOF OF MICROBE DIA 

4820
04:14:45,480 --> 04:14:46,840
SO WHEN YOU LOOKED AT 

4821
04:14:46,840 --> 04:14:50,880
INDIVIDUALS WE CAN SEE DISTINCT 

4822
04:14:50,880 --> 04:14:53,160
MICRO

4823
04:14:53,160 --> 04:14:55,640
MICROBAL SIGNATURES. 

4824
04:14:55,640 --> 04:14:57,520
SO, KIND OF TWO POINTS, IF YOU 

4825
04:14:57,520 --> 04:15:01,280
LOOK AGAIN AT THESE FORMULA FED 

4826
04:15:01,280 --> 04:15:03,240
INFANTS JUST LIKE HOST GENE 

4827
04:15:03,240 --> 04:15:05,080
EXPRESSION THE MICROBIOME HAS 

4828
04:15:05,080 --> 04:15:06,440
BEEN PUSHED TO BE VERY SIMILAR 

4829
04:15:06,440 --> 04:15:08,760
SO WE ASKED, CAN WE USE THESE 

4830
04:15:08,760 --> 04:15:11,640
DIFFERENCES IN THE MICROBIOTA TO

4831
04:15:11,640 --> 04:15:14,080
PREDICT DIFFERENCES IN HOST GENE

4832
04:15:14,080 --> 04:15:14,440
EXPRESSION. 

4833
04:15:14,440 --> 04:15:16,640
AGAIN, USING THE DATA FROM THE 

4834
04:15:16,640 --> 04:15:22,800
CHAP KIN PAPER, WE HAD THE HOST 

4835
04:15:22,800 --> 04:15:24,640
TRANSCRIPTOME AND DID SHOTGUN 

4836
04:15:24,640 --> 04:15:28,440
SEQUENCINGS AT THIS TIME 4-5-4 

4837
04:15:28,440 --> 04:15:31,640
AND DON'T NOVA SEEK AND OTHER 

4838
04:15:31,640 --> 04:15:34,280
MORE SOPHISTICATED METHODS SO 

4839
04:15:34,280 --> 04:15:38,640
WHEN WE DID THE MICROBIOME OR 

4840
04:15:38,640 --> 04:15:45,640
META GENOME SEQUENCING WE LOOKED

4841
04:15:45,640 --> 04:15:49,760
AT GENE CATEGORIES AND WE 

4842
04:15:49,760 --> 04:15:51,240
FOCUSED ON VIRULENCE GENES AND 

4843
04:15:51,240 --> 04:15:53,800
THEN IN TERMS OF THE HOST 

4844
04:15:53,800 --> 04:15:57,680
SIGNATURES, WE LOOKED AT RANDOM 

4845
04:15:57,680 --> 04:15:59,520
GENES OR INTESTINAL BIOLOGY 

4846
04:15:59,520 --> 04:16:01,040
GENES AND BE IMMUNITY AND 

4847
04:16:01,040 --> 04:16:03,720
DEFENSE GENES AND THERE WAS A 

4848
04:16:03,720 --> 04:16:06,840
VERY ROBUST RELATIONSHIP BETWEEN

4849
04:16:06,840 --> 04:16:13,280
THE MICROBAL GENES AN BABY 

4850
04:16:13,280 --> 04:16:15,440
DEFENSE GENES AND KNOB 

4851
04:16:15,440 --> 04:16:17,720
RELATIONSHIP WITH RAMP COME 

4852
04:16:17,720 --> 04:16:20,400
GENES AND WEAK WITH INTESTINAL 

4853
04:16:20,400 --> 04:16:21,760
BIOLOGY GENES AND FIRST TIME WE 

4854
04:16:21,760 --> 04:16:23,840
COULD LOOK AT WHETHER SIGNATURES

4855
04:16:23,840 --> 04:16:26,120
IN THE MICROBES WERE POTENTIALLY

4856
04:16:26,120 --> 04:16:31,160
CROSS TALKING WITH THE BABY. 

4857
04:16:31,160 --> 04:16:34,040
AND SO THESE ARE JUST 11 BABY 

4858
04:16:34,040 --> 04:16:36,440
IMMUNITY DEFENSE MUCOSAL GENES 

4859
04:16:36,440 --> 04:16:40,720
THAT WERE MOST HIGHLY RELATED 

4860
04:16:40,720 --> 04:16:45,280
STATISTICALLY WITH MAY BE ROBAL 

4861
04:16:45,280 --> 04:16:47,200
VIRULENCE GENES SO EVEN THOUGH 

4862
04:16:47,200 --> 04:16:49,480
IT'S A RELATIONSHIP WITH 

4863
04:16:49,480 --> 04:16:51,080
VIRULENCE GENES IT IMPACT 

4864
04:16:51,080 --> 04:16:53,440
WHETHER THE BABIES WERE FORMULA 

4865
04:16:53,440 --> 04:16:56,920
OR BREASTFED INFANTS SO 

4866
04:16:56,920 --> 04:16:58,960
UPREGULATED WERE SOME OF THE 

4867
04:16:58,960 --> 04:17:02,680
INTESTAL PEAR STAL ASSIST, ALSO 

4868
04:17:02,680 --> 04:17:07,320
ACTIVE . . .  MEDIATED MICROBEAL

4869
04:17:07,320 --> 04:17:07,720
DEFENSE. 

4870
04:17:07,720 --> 04:17:26,000
YOU CAN SEE MANY OF THESE ARE IN

4871
04:17:26,000 --> 04:17:29,040
THERE'S A DOWN REGULATION OF 

4872
04:17:29,040 --> 04:17:31,440
THAT INFLAMMATION. 

4873
04:17:31,440 --> 04:17:34,880
SO CONCLUDING AN IMPLICATIONS 

4874
04:17:34,880 --> 04:17:38,640
BELIEVE THAT THE EX-FOLIOS ME 

4875
04:17:38,640 --> 04:17:40,440
REPRESENTS THE RESERVATION FROM 

4876
04:17:40,440 --> 04:17:44,440
THE SMALL AND LARGE INTESTINE 

4877
04:17:44,440 --> 04:17:46,520
AND YOU CAN PROBE HOST 

4878
04:17:46,520 --> 04:17:51,640
INTERACTIONS SPRI A EX-FOLIOME. 

4879
04:17:51,640 --> 04:17:53,840
THIS COULD BE USED FOR GROUP 

4880
04:17:53,840 --> 04:17:56,560
COMPARISONS BUT THIS IS A 

4881
04:17:56,560 --> 04:18:03,440
PERFECT SITUATION SO EACH 

4882
04:18:03,440 --> 04:18:04,360
INDIVIDUAL COULD HAVE A 

4883
04:18:04,360 --> 04:18:04,640
BASELINE. 

4884
04:18:04,640 --> 04:18:06,240
YOU COULD DO YOUR INTERVENTION 

4885
04:18:06,240 --> 04:18:10,680
AND LOOK AT A WASHOUT PERIOD, SO

4886
04:18:10,680 --> 04:18:12,600
YOU HAVE TO COLLECT THE SAMPLES 

4887
04:18:12,600 --> 04:18:12,880
CORRECTLY. 

4888
04:18:12,880 --> 04:18:14,040
THEY NEED TO BE COLLECTED INTO 

4889
04:18:14,040 --> 04:18:14,840
THE SOLUTION. 

4890
04:18:14,840 --> 04:18:18,440
THEY CAN'T BE FROZEN OR BUT ONCE

4891
04:18:18,440 --> 04:18:19,840
THEY'RE IN THE SOLUTION THEY'RE 

4892
04:18:19,840 --> 04:18:21,920
STABLE BUT WE REALLY THINK THIS 

4893
04:18:21,920 --> 04:18:24,000
HAS AN OPPORTUNITY TO BE USED 

4894
04:18:24,000 --> 04:18:27,400
ACROSS THE LIFE SPAN SO JUST TO 

4895
04:18:27,400 --> 04:18:29,840
THANK MY COLLABORATORS AT TEXAS 

4896
04:18:29,840 --> 04:18:32,640
A & M, PEOPLE IN MY LABORATORY 

4897
04:18:32,640 --> 04:18:34,200
AS WELL AS OUR FRIENDS. 

4898
04:18:34,200 --> 04:18:37,680
THANK YOU. 

4899
04:18:37,680 --> 04:18:42,920
>> THANK YOU DOCTOR FOR THAT 

4900
04:18:42,920 --> 04:18:46,480
TALK COMPARING FORMULA AND 

4901
04:18:46,480 --> 04:18:47,200
BREASTFED BABIES. 

4902
04:18:47,200 --> 04:18:48,920
I WOULD ASK THE PARTICIPANTS IF 

4903
04:18:48,920 --> 04:18:50,640
YOU HAVE QUESTIONS PLEASE SEND 

4904
04:18:50,640 --> 04:18:52,240
THEM OUT FOR OUR PANEL 

4905
04:18:52,240 --> 04:18:52,520
DISCUSSION. 

4906
04:18:52,520 --> 04:18:56,480
WE ARE VERY HONORED FOR OUR NEXT

4907
04:18:56,480 --> 04:18:58,480
SPEAKER DR. STEVE ENTOWNSEND 

4908
04:18:58,480 --> 04:18:59,240
FROM VANDERBILT. 

4909
04:18:59,240 --> 04:19:01,640
HE'S GOING TO TALK ABOUT THE 

4910
04:19:01,640 --> 04:19:05,280
APPLICATION OF TWO TIME FUCOSYL 

4911
04:19:05,280 --> 04:19:07,720
LACTOSE IN PREVENTING INTESTINAL

4912
04:19:07,720 --> 04:19:07,960
INJURY. 

4913
04:19:07,960 --> 04:19:09,360
>> THANK YOU FOR THE 

4914
04:19:09,360 --> 04:19:11,480
INTRODUCTION AND I APPRECIATE 

4915
04:19:11,480 --> 04:19:12,960
ALL OF THE GREAT PRESENTATIONS I

4916
04:19:12,960 --> 04:19:15,040
HEARD TODAY AND LOOK FORWARD. 

4917
04:19:15,040 --> 04:19:17,280
I HAVE TO DISCLOSURES. 

4918
04:19:17,280 --> 04:19:21,200
NEITHER DOES MY COLLABORATOR 

4919
04:19:21,200 --> 04:19:29,520
DR. FONG, SO WE ARE GOING TO 

4920
04:19:29,520 --> 04:19:36,080
TALK ABOUT SACK RIDES, I'VE BEEN

4921
04:19:36,080 --> 04:19:38,040
ON THE FACULTY OF VANDERBILT 

4922
04:19:38,040 --> 04:19:40,400
EIGHT YEARS AND OUR GROUP HAS 

4923
04:19:40,400 --> 04:19:42,440
HISTORICALLY BEEN INTERESTED IN 

4924
04:19:42,440 --> 04:19:44,480
MILK SCIENCE TRYING TO TEASE 

4925
04:19:44,480 --> 04:19:46,640
WHAT THE MOLECULES DO IN THE 

4926
04:19:46,640 --> 04:19:49,680
CONTEXT OF PREVENTING ILLNESS IN

4927
04:19:49,680 --> 04:19:49,920
BABIES. 

4928
04:19:49,920 --> 04:19:52,440
WE HAVE BEEN INTERESTED IN 

4929
04:19:52,440 --> 04:19:55,120
EXTENDING THOSE PARADIGMS AND 

4930
04:19:55,120 --> 04:19:57,240
RESEARCHING THE POWER OF HUMAN 

4931
04:19:57,240 --> 04:20:00,360
MILK SACK RIDES TO REPAIR DAMAGE

4932
04:20:00,360 --> 04:20:03,640
FROM CHEMOTHERAPY AND OTHER 

4933
04:20:03,640 --> 04:20:04,240
ISSUES. 

4934
04:20:04,240 --> 04:20:06,600
SO WITH THAT I'LL GIVE A BRIEF 

4935
04:20:06,600 --> 04:20:09,040
DISCUSSION ON SOME OF THE 

4936
04:20:09,040 --> 04:20:10,840
MACROMOLECULES OF HUMAN MILK. 

4937
04:20:10,840 --> 04:20:13,560
TERRENCE OUT THAT MY GROUP TOOK 

4938
04:20:13,560 --> 04:20:17,320
AN INTEREST IN MACROMOLECULES IN

4939
04:20:17,320 --> 04:20:19,440
SACK RIDES BECAUSE THEY'RE NOT 

4940
04:20:19,440 --> 04:20:22,240
PRESENT IN COW MILK SO WE 

4941
04:20:22,240 --> 04:20:24,240
THOUGHT IF WE COULD CHARACTERIZE

4942
04:20:24,240 --> 04:20:26,280
SOME OF THE ACTIVITY OF THESE 

4943
04:20:26,280 --> 04:20:34,760
SACK RIDES HMO'S WE WOULD HAVE A

4944
04:20:34,760 --> 04:20:37,880
KEY WAY TO DETERMINE WERE 

4945
04:20:37,880 --> 04:20:39,920
BREASTFED BABIES ARE SO HELP 

4946
04:20:39,920 --> 04:20:40,280
THEY. 

4947
04:20:40,280 --> 04:20:42,160
TURNS OUT THAT HUMANS PRODUCE 

4948
04:20:42,160 --> 04:20:46,280
ABOUT 8-20 GRAMS PER LITER OF 

4949
04:20:46,280 --> 04:21:02,600
SACK RIDES IN MILK AND WE HAVE 

4950
04:21:02,600 --> 04:21:02,880
T

4951
04:21:02,880 --> 04:21:04,240
THESE HAVE BEEN ON THE SCENE 

4952
04:21:04,240 --> 04:21:06,120
ABOUT 40 YEARS AND IF YOU TALK 

4953
04:21:06,120 --> 04:21:07,680
TO GREAT PEOPLE LIKE ART OR DAVE

4954
04:21:07,680 --> 04:21:09,840
THEY WOULD TELL YOU BACK IN THE 

4955
04:21:09,840 --> 04:21:12,280
8 OLS AND 90s, PEOPLE IN THE 

4956
04:21:12,280 --> 04:21:13,560
COMMUNITY WEREN'T REALLY 

4957
04:21:13,560 --> 04:21:15,920
INTERESTED IN FIGURING OUT WHAT 

4958
04:21:15,920 --> 04:21:18,120
THESE COMPOUNDS DO BUT FOLKS 

4959
04:21:18,120 --> 04:21:21,080
LIKE DR. MURROW AND OTHERS TURNS

4960
04:21:21,080 --> 04:21:23,240
OUT DURING THAT TIME PERIOD, 

4961
04:21:23,240 --> 04:21:27,520
EARLY 80S, 90s, WE DISCOVERED 

4962
04:21:27,520 --> 04:21:32,160
THESE COMPOUNDS WERE PRE-BIOTICS

4963
04:21:32,160 --> 04:21:33,800
SO THEY . . .  GROWTH ADVANTAGE 

4964
04:21:33,800 --> 04:21:38,880
OVER PATHOGENS, THEY'RE 

4965
04:21:38,880 --> 04:21:44,240
ANTI-ADHESIVE ABLE TO PREVENT A 

4966
04:21:44,240 --> 04:21:48,720
PATHOGEN BIONING TO THE SYSTEM. 

4967
04:21:48,720 --> 04:21:51,440
OUR GROUP AND OTHERS HAVE TEASED

4968
04:21:51,440 --> 04:21:56,600
HOW THEY'RE ANTI-MICROBAL 

4969
04:21:56,600 --> 04:22:03,640
AGENTS. 

4970
04:22:03,640 --> 04:22:05,280
EVERYTHING THAT WE DISCUSSED ON 

4971
04:22:05,280 --> 04:22:09,120
THE LAST SLIDE LAST TO DO WITH 

4972
04:22:09,120 --> 04:22:09,480
MICROORGANISMS. 

4973
04:22:09,480 --> 04:22:11,720
SO IT TURNS OUT THESE COMPOUNDS 

4974
04:22:11,720 --> 04:22:13,240
ACTUALLY HAVE SOME EFFECTS ON 

4975
04:22:13,240 --> 04:22:16,560
HUMAN CELLS, SO IT'S KNOWN IN 

4976
04:22:16,560 --> 04:22:18,120
THE LITERATURE THESE COMPOUNDS 

4977
04:22:18,120 --> 04:22:20,520
ARE MODULATORS AND ASSISTING IN 

4978
04:22:20,520 --> 04:22:21,960
BRAIN DEVELOPMENT AND HAVE AN 

4979
04:22:21,960 --> 04:22:23,120
IMPORTANT ROLE IN THE 

4980
04:22:23,120 --> 04:22:25,040
DEVELOPMENT OF THE EPITHELIAL 

4981
04:22:25,040 --> 04:22:27,440
LAYER SO WITH THESE DIVERSE 

4982
04:22:27,440 --> 04:22:29,040
ACTIVITIES IN MIND WE WANTED TO 

4983
04:22:29,040 --> 04:22:31,240
START TRANCE LATING TO THE 

4984
04:22:31,240 --> 04:22:33,040
BIOLOGY AND BASIC CHEMISTRY 

4985
04:22:33,040 --> 04:22:34,760
THAT'S BEEN ABSORBED WITH THESE 

4986
04:22:34,760 --> 04:22:37,960
COMPOUNDS TO SEE IF WE COULD 

4987
04:22:37,960 --> 04:22:38,920
TRANSLATE TO HELP. 

4988
04:22:38,920 --> 04:22:41,560
SO WE STARTED OUT WITH A REAL 

4989
04:22:41,560 --> 04:22:44,240
YINTING TOOL COMPOUNDS WE 

4990
04:22:44,240 --> 04:22:46,680
STARTED WORKING WITH LACTOSECHY 

4991
04:22:46,680 --> 04:22:48,960
THINK FOR MOST PEOPLE THE HMO 

4992
04:22:48,960 --> 04:22:52,800
YOU WOULD KNOW MOST ABOUT. 

4993
04:22:52,800 --> 04:22:58,840
SO, WITHOUT QUESTION IS THE MOST

4994
04:22:58,840 --> 04:23:00,840
COMMON ILLEGAL SACK RIDE SEEN IN

4995
04:23:00,840 --> 04:23:03,320
HUMAN MILK. 

4996
04:23:03,320 --> 04:23:08,840
THE TYPES WILL SACK RIDES IN OUR

4997
04:23:08,840 --> 04:23:11,240
BODY ARE CONSEQUENCE CONSEQUENCE

4998
04:23:11,240 --> 04:23:13,840
OF MACHINERY WE PROCESSES SO IF 

4999
04:23:13,840 --> 04:23:16,640
YOU'RE A SECRETER YOU GENERATE 

5000
04:23:16,640 --> 04:23:18,760
ENZYMES THAT WILL GENERATE 

5001
04:23:18,760 --> 04:23:22,320
COMPOUNDS THAT HAVE SIMILAR 

5002
04:23:22,320 --> 04:23:24,720
STRUCTURES TO TWO PRIME FL SO 

5003
04:23:24,720 --> 04:23:26,320
THEY HAVE GLUCOSE CONNECTED TO 

5004
04:23:26,320 --> 04:23:28,440
SUGARS IN THIS BOX AND SECRETER 

5005
04:23:28,440 --> 04:23:32,760
TWO PRIME O IS THE MOST COMMON 

5006
04:23:32,760 --> 04:23:33,240
HMO. 

5007
04:23:33,240 --> 04:23:36,280
LOOK AT NON-SECRETER MILK TURNS 

5008
04:23:36,280 --> 04:23:39,560
OUT THEY HAVE MILK THAT'S 

5009
04:23:39,560 --> 04:23:45,000
DOMINATED . . .  SO I PROVIDE 

5010
04:23:45,000 --> 04:23:47,120
THIS AS A CLARIFYING. 

5011
04:23:47,120 --> 04:23:50,120
I'M SORRY TO SEE COMMERCIALS 

5012
04:23:50,120 --> 04:23:53,960
TALK ABOUT TWO PRIME FO IT'S THE

5013
04:23:53,960 --> 04:23:56,080
MAJORITY GLOBALLY. 

5014
04:23:56,080 --> 04:23:57,680
NOW THIS POINT OF THE GAME WE 

5015
04:23:57,680 --> 04:23:59,120
TURN INTO THE MORE CURRENT 

5016
04:23:59,120 --> 04:24:02,120
RESEARCH SO I DRAW ATTENTION TO 

5017
04:24:02,120 --> 04:24:05,360
THE CONCEPT OF ORAL MICHAEL 

5018
04:24:05,360 --> 04:24:06,240
SIGHTIES. 

5019
04:24:06,240 --> 04:24:08,640
IT REFERENCE TO I GUESS THE 

5020
04:24:08,640 --> 04:24:12,400
DAMAGE ON THE MUCOSAL SURFACE 

5021
04:24:12,400 --> 04:24:15,880
USUALLY IN THE ORAL CAVITY 

5022
04:24:15,880 --> 04:24:18,200
USUALLY SIDE EFFECT OF 

5023
04:24:18,200 --> 04:24:20,760
CHEMOTHERAPY, A WOMAN 

5024
04:24:20,760 --> 04:24:23,840
APPROACHING TEN YEARS OF BUT 

5025
04:24:23,840 --> 04:24:26,240
ORAL MIKE SIGHTIES WAS PAINFUL 

5026
04:24:26,240 --> 04:24:27,680
AND THE WORSE PART OF HER 

5027
04:24:27,680 --> 04:24:29,920
EXPERIENCE WITH CHEMOTHERAPY. 

5028
04:24:29,920 --> 04:24:31,440
SO, FRONTIER TYPE OF TREATMENT 

5029
04:24:31,440 --> 04:24:35,880
WHEN IT COMES TO PREVENTING OR 

5030
04:24:35,880 --> 04:24:37,760
DEALING IS THE IDEA THAT WE CAN 

5031
04:24:37,760 --> 04:24:39,760
I GUESS TARGETEN DETERMINE AL 

5032
04:24:39,760 --> 04:24:41,640
GROWTH FACTOR RESETTER SO IT'S 

5033
04:24:41,640 --> 04:24:44,920
BEEN SHOWN IF YOU TARGET THIS 

5034
04:24:44,920 --> 04:24:48,120
RESETTER YOU CAN OFTEN INDUCE 

5035
04:24:48,120 --> 04:24:51,480
DISEASE FORMATION DIRECTLY 

5036
04:24:51,480 --> 04:24:53,240
TARGETING INTESTINAL MUCOSAL 

5037
04:24:53,240 --> 04:24:54,040
HEALING. 

5038
04:24:54,040 --> 04:24:57,840
BASED ON THE LITERATURE WHAT I 

5039
04:24:57,840 --> 04:25:03,040
DESCRIBED EARLIER, WE 

5040
04:25:03,040 --> 04:25:07,800
HYPOTHESIZE THEY COULD ACTIVATE 

5041
04:25:07,800 --> 04:25:13,360
AND BE USED TO PREVENT MIKE US 

5042
04:25:13,360 --> 04:25:14,360
SIGHTIES. 

5043
04:25:14,360 --> 04:25:15,000
SO. 

5044
04:25:15,000 --> 04:25:17,320
THIS VALIDATES THE PRINCIPLE OF 

5045
04:25:17,320 --> 04:25:20,120
THAT THEORY THAT WE OBSERVE WE 

5046
04:25:20,120 --> 04:25:22,760
CAN USE PRIME LACTOSE TO 

5047
04:25:22,760 --> 04:25:26,040
SOMETIME LATE ACTIVATION OF THE 

5048
04:25:26,040 --> 04:25:30,360
EG RESETTER. 

5049
04:25:30,360 --> 04:25:32,120
WE WANTED TO STUDY WHAT THIS 

5050
04:25:32,120 --> 04:25:34,560
COULD MEAN IN AN ANIMAL MODEL SO

5051
04:25:34,560 --> 04:25:39,920
WE DECIDED TO WORK WITH THE TNBS

5052
04:25:39,920 --> 04:25:43,320
ACID, A MODELED YOU CAN USE TO 

5053
04:25:43,320 --> 04:25:48,360
REALLY I GUESS SIMULATE CRONOS 

5054
04:25:48,360 --> 04:25:50,040
DISEASE IN MICE. 

5055
04:25:50,040 --> 04:25:53,120
WE ARE GOING TO GIVE MICE FOUR 

5056
04:25:53,120 --> 04:25:57,240
WEEKS FOR LACTOSE IN WATER AND 

5057
04:25:57,240 --> 04:26:00,360
ZERO WE ARE GOING TO GIVE 

5058
04:26:00,360 --> 04:26:02,080
THEM . . .  ACID. 

5059
04:26:02,080 --> 04:26:03,600
WHAT WAS COOL ABOUT THIS 

5060
04:26:03,600 --> 04:26:05,280
EXPERIMENT WE CLEARLY SAW IN 

5061
04:26:05,280 --> 04:26:06,960
COMPARISON TO OUR CONTROL IF WE 

5062
04:26:06,960 --> 04:26:09,680
GAVE THESE MICE THIS CLIETIES 

5063
04:26:09,680 --> 04:26:11,440
INDUCING AGENT IN THE PRESENCE 

5064
04:26:11,440 --> 04:26:13,440
OF TWO PRIME LACTOSE WE CAN 

5065
04:26:13,440 --> 04:26:16,600
SIGNIFICANTLY REDUCE THE AMOUNT 

5066
04:26:16,600 --> 04:26:18,360
OF INTESTINAL INJURY. 

5067
04:26:18,360 --> 04:26:28,560
WE CAN SEE WE HAVE A NEGATIVE 

5068
04:26:28,560 --> 04:26:28,920
CONTROL. 

5069
04:26:28,920 --> 04:26:30,880
NOW, MOVING FORWARD, YOU KNOW, 

5070
04:26:30,880 --> 04:26:32,800
WE WENT IN TO GO AHEAD AND 

5071
04:26:32,800 --> 04:26:36,120
VALIDATE WE WERE HITTING THE EGF

5072
04:26:36,120 --> 04:26:37,960
RESETTER SO WE PERFORMED THE 

5073
04:26:37,960 --> 04:26:40,080
EXPERIMENT INVOLVING THE WILD 

5074
04:26:40,080 --> 04:26:42,440
TYPE OF MICE, KNOCKOUT LACKING 

5075
04:26:42,440 --> 04:26:45,040
THE GEFR INTESTINAL EPITHELIAL 

5076
04:26:45,040 --> 04:26:49,040
CELLS MOST CLEARLY FROM THE DATA

5077
04:26:49,040 --> 04:26:52,240
TWO TIME LACTOSE IS ABLE TO 

5078
04:26:52,240 --> 04:26:55,960
SOMETIME LATE THE RESETTER AND 

5079
04:26:55,960 --> 04:27:00,400
THIS IS LIKELY KEY MECHANISM 

5080
04:27:00,400 --> 04:27:02,200
PREVENTING CLIETIES. 

5081
04:27:02,200 --> 04:27:05,040
ALTHOUGH WE KNOW EGF RESETTERS 

5082
04:27:05,040 --> 04:27:08,600
ARE AT PLAY WE WANTED TO 

5083
04:27:08,600 --> 04:27:11,880
EVALUATE WHAT EFFECTS THE 

5084
04:27:11,880 --> 04:27:14,720
MICROBIOME AND FILMS MIGHT HAVE 

5085
04:27:14,720 --> 04:27:33,360
ON THE PREVENTION OFITIS. 

5086
04:27:33,360 --> 04:27:36,280
SO, WE NOTICED THAT WE FOUND 

5087
04:27:36,280 --> 04:27:38,280
THAT TWO PLIEM IT HAS THE 

5088
04:27:38,280 --> 04:27:41,200
ABILITY TO INCREASE THE COUNTS 

5089
04:27:41,200 --> 04:27:44,920
OF MICROORGANISMS ASSOCIATED 

5090
04:27:44,920 --> 04:27:49,400
WITH INFLATION GOING TO 

5091
04:27:49,400 --> 04:27:51,680
ENCOURAGE CLIETIES AN OTHER 

5092
04:27:51,680 --> 04:27:52,760
INFORMS OF INFLAMMATION. 

5093
04:27:52,760 --> 04:27:54,640
NOW AT THIS STAGE OF THE GAME WE

5094
04:27:54,640 --> 04:27:56,400
KNOW A LITTLE BIT FROM OUR 

5095
04:27:56,400 --> 04:27:57,800
RESEARCH FROM THE PRECEDENT 

5096
04:27:57,800 --> 04:28:00,240
AVAILABLE IN LITERATURE, WE KNOW

5097
04:28:00,240 --> 04:28:03,040
THAT WE HAVE SPECIFIC PROTEIN 

5098
04:28:03,040 --> 04:28:04,920
TARGETS BUT WE ALSO KNOW THAT WE

5099
04:28:04,920 --> 04:28:16,640
HAVE SORT OF A THINKING ABOUT 

5100
04:28:16,640 --> 04:28:20,480
SOMETHING INITIATED BY TEAM THEY

5101
04:28:20,480 --> 04:28:22,400
ARE. 

5102
04:28:22,400 --> 04:28:23,800
THIS IS A COOL EXPERIMENT. 

5103
04:28:23,800 --> 04:28:26,480
WE USE TED MODEL OF 

5104
04:28:26,480 --> 04:28:27,160
CHEMOTHERAPY. 

5105
04:28:27,160 --> 04:28:29,680
THIS IS A NICE REPRESENTATION OF

5106
04:28:29,680 --> 04:28:32,880
HIGH DOSE CHEMOTHERAPY FOR 

5107
04:28:32,880 --> 04:28:33,160
HUMANS.  

5108
04:28:33,160 --> 04:28:35,040
WHEN HUMAN BEINGS GET CHEMO OR 

5109
04:28:35,040 --> 04:28:39,320
RADIO THERAPY IN GENERAL WE SEE 

5110
04:28:39,320 --> 04:28:40,600
U BIG TUESDAY DAMAGE INTESTINAL 

5111
04:28:40,600 --> 04:28:42,480
LINING SO WE THOUGHT WE COULD 

5112
04:28:42,480 --> 04:28:45,960
REPAIR OR PREVENT DAMAGE CAUSED 

5113
04:28:45,960 --> 04:28:46,960
BY CHEMO. 

5114
04:28:46,960 --> 04:28:49,200
SO, RIGHT OFF THE BAT, YOU KNOW 

5115
04:28:49,200 --> 04:28:51,400
IT WAS PRETTY COOL WE OBSERVED 

5116
04:28:51,400 --> 04:28:54,400
THAT LACTOSE IS ABLE TO PREVENT 

5117
04:28:54,400 --> 04:28:56,040
CHEMOTHERAPY FROM INHIBITING THE

5118
04:28:56,040 --> 04:28:58,760
GROWTH OF HEALTHY CELLS WHEN 

5119
04:28:58,760 --> 04:29:00,120
THEY'RE EXPOSED TO CHEMOTHERAPY 

5120
04:29:00,120 --> 04:29:03,720
BUT INTERESTINGLY WHEN IT COMES 

5121
04:29:03,720 --> 04:29:07,040
TO TRANSFORM CELLS THIS WAS OUR 

5122
04:29:07,040 --> 04:29:09,600
FIRST REALLY COOL LEAD TO LET US

5123
04:29:09,600 --> 04:29:12,560
KNOW WE HAVE SOMETHING NICE 

5124
04:29:12,560 --> 04:29:13,240
BREWING. 

5125
04:29:13,240 --> 04:29:15,360
NOW MOVING FORWARD WE INITIATED 

5126
04:29:15,360 --> 04:29:19,360
A STUDY WHERE WE EVALUATED THE 

5127
04:29:19,360 --> 04:29:20,720
INFLAMMATION OF THE SMALL SATTIN

5128
04:29:20,720 --> 04:29:25,040
OF A MOUSE COHORT WITH 

5129
04:29:25,040 --> 04:29:26,240
CHEMOTHERAPY EXPOSURE. 

5130
04:29:26,240 --> 04:29:29,240
SO IN THIS CASE PRE-TREATMENT 

5131
04:29:29,240 --> 04:29:32,160
WITH TWO PRIME FL RODRIGUEZED 

5132
04:29:32,160 --> 04:29:33,120
INFLAMMATION SIGNIFICANTLY. 

5133
04:29:33,120 --> 04:29:36,520
IT'S IMPORTANT TO NOTE THAT 

5134
04:29:36,520 --> 04:29:38,000
COTREATMENT OCCURRED AFTER 

5135
04:29:38,000 --> 04:29:39,160
CHEMOTHERAPY WAS INITIATED. 

5136
04:29:39,160 --> 04:29:40,320
DID NOT HAVE A SIGNIFICANT 

5137
04:29:40,320 --> 04:29:47,440
EFFECT IN REDUCING INFLAMMATION.

5138
04:29:47,440 --> 04:29:50,480
NOW COMPARED WITH THE 

5139
04:29:50,480 --> 04:29:53,520
CHEMOTHERAPY FOR 5 FU TREATMENT 

5140
04:29:53,520 --> 04:29:55,480
ALONE WE KNOW THAT TREATMENT IS 

5141
04:29:55,480 --> 04:29:56,760
ABLE TO PROTECT AGAINST BODY 

5142
04:29:56,760 --> 04:29:57,440
WEIGHT LOSS. 

5143
04:29:57,440 --> 04:30:01,000
WE SHOW THAT IT'S ABLE TO 

5144
04:30:01,000 --> 04:30:03,680
AMELIORATE INFLAMMATION SCORE. 

5145
04:30:03,680 --> 04:30:06,720
SO YOU WOULD THINK IF WE EXPOSE 

5146
04:30:06,720 --> 04:30:09,600
THE MOUSEN THEY'LL YUM TO AN 

5147
04:30:09,600 --> 04:30:12,880
AGENT WE WOULD SEE US RAISE AND 

5148
04:30:12,880 --> 04:30:17,240
INFLAMMATION IN THE SATTIN AND 

5149
04:30:17,240 --> 04:30:18,960
ABNORMALITIES COULD BE DECREASED

5150
04:30:18,960 --> 04:30:22,640
SO LACTOSE AS PROPHYLAXIS. 

5151
04:30:22,640 --> 04:30:24,800
NOW THE HOME STREP WITH THE LAST

5152
04:30:24,800 --> 04:30:27,440
TWO OR THREE STRIDES, IT TURNS 

5153
04:30:27,440 --> 04:30:29,920
OUT THAT IT'S REALLY IMPORTANT I

5154
04:30:29,920 --> 04:30:32,760
GUESS THAT THE MUCOSAL LAYER FOR

5155
04:30:32,760 --> 04:30:35,240
THE TRAINEES IN THE AUDIENCE IF 

5156
04:30:35,240 --> 04:30:37,920
YOU THINK ABOUT OUR MUCOSAL 

5157
04:30:37,920 --> 04:30:40,480
LAYER IT'S SUPER IMPORTANT IN 

5158
04:30:40,480 --> 04:30:43,080
PROTECTING SURFACES AGAINST 

5159
04:30:43,080 --> 04:30:45,120
BACTERIAL INFECTIONS VIRAL 

5160
04:30:45,120 --> 04:30:48,120
ASSAULTS AND MECHANICAL DAMAGE 

5161
04:30:48,120 --> 04:30:53,280
TO G. I.TRACT SO THERE'S THE 

5162
04:30:53,280 --> 04:30:56,960
CONCEPT OF THE GOBLET CELL. 

5163
04:30:56,960 --> 04:31:00,160
WITH CHEMOTHERAPY THESE CELLS 

5164
04:31:00,160 --> 04:31:02,000
GET DAMAGED. 

5165
04:31:02,000 --> 04:31:05,240
BUT IF WE TREATED WITH TWO NAME 

5166
04:31:05,240 --> 04:31:07,760
FL FOR 36-7 DAYS OR EXPERIMENT 

5167
04:31:07,760 --> 04:31:10,120
WE WERE ABLE TO MAINTAIN THE 

5168
04:31:10,120 --> 04:31:16,120
COUNT OF GOBLET

5169
04:31:16,120 --> 04:31:18,160
>> NOW IT TURNS OUT THAT AGAIN

5170
04:31:18,160 --> 04:31:21,120
GETTING BACK TO THE MICROBIOME

5171
04:31:21,120 --> 04:31:24,280
-- BASICALLY IT'S ABLE TO

5172
04:31:24,280 --> 04:31:26,480
DECREASE CHEMO THERAPEUTIC

5173
04:31:26,480 --> 04:31:30,760
INDUCED ALTERATIONS OF THE

5174
04:31:30,760 --> 04:31:31,840
INTESTINAL MICROBIOTA.

5175
04:31:31,840 --> 04:31:35,880
SO THIS IS SUPER IMPORTANT

5176
04:31:35,880 --> 04:31:36,640
BECAUSE IT IS DEFINITELY PRESENT

5177
04:31:36,640 --> 04:31:39,160
IN THE LITERATURE THAT

5178
04:31:39,160 --> 04:31:40,600
CHEMOTHERAPY IS ASSOCIATED WITH

5179
04:31:40,600 --> 04:31:43,080
THESE PATIENTS SO WE WANTED TO

5180
04:31:43,080 --> 04:31:48,040
EVALUATE OVER-ALL FECAL BACTERIA

5181
04:31:48,040 --> 04:31:50,560
COMPOSITION -- AND SO I'M

5182
04:31:50,560 --> 04:31:53,840
TALKING ABOUT -- SHANNON THERE

5183
04:31:53,840 --> 04:31:56,720
AND IT WAS OBSERVED THAT

5184
04:31:56,720 --> 04:31:59,120
PRETREATMENT -- WERE ABLE TO

5185
04:31:59,120 --> 04:32:02,640
ELICIT A NICE SHIFT BACK TO

5186
04:32:02,640 --> 04:32:05,160
NORMAL GIVEN THE CHEMO

5187
04:32:05,160 --> 04:32:07,240
THERAPEUTIC AGENT.

5188
04:32:07,240 --> 04:32:08,800
NOW WE CAN AGAIN HIT HOME THE

5189
04:32:08,800 --> 04:32:11,520
POINT THAT IF WE'RE EXPOSING

5190
04:32:11,520 --> 04:32:13,120
THESE MICE WHERE THEY GET THE

5191
04:32:13,120 --> 04:32:14,840
CHEMO WE SEE THAT WE CONTINUE TO

5192
04:32:14,840 --> 04:32:18,680
UP REGULATOR MAINTAIN SOME

5193
04:32:18,680 --> 04:32:20,080
ACCEPTS OF NORMALITY.

5194
04:32:20,080 --> 04:32:23,920
INCREASE THE COUNTS OF

5195
04:32:23,920 --> 04:32:28,000
ANTIINFLAMMATORY BAC -- BACTERIA
IS

5196
04:32:28,000 --> 04:32:28,880
GOOD.

5197
04:32:28,880 --> 04:32:31,440
WITH THAT THAT WAS A RAPID FIRE

5198
04:32:31,440 --> 04:32:33,800
OF THIS RESEARCH PROGRAM IN 13

5199
04:32:33,800 --> 04:32:34,600
AND A HALF MINUTES.

5200
04:32:34,600 --> 04:32:47,400
I WANT TO THANK DR. -- FONG

5201
04:32:47,400 --> 04:32:48,040
YOUNG.

5202
04:32:48,040 --> 04:32:50,040
AND I APPRECIATE YOUR ATTENTION.

5203
04:32:50,040 --> 04:32:51,040
>> THANK YOU VERY MUCH.

5204
04:32:51,040 --> 04:32:54,200
THAT WAS A VERY IMPRESSIVE TALK

5205
04:32:54,200 --> 04:32:58,800
ON THE ROLE OF TWO PRIME FL AND

5206
04:32:58,800 --> 04:33:00,840
PREVENTING INTESTINAL INJURY.

5207
04:33:00,840 --> 04:33:03,040
WHICH HAS THE POTENTIAL FOR

5208
04:33:03,040 --> 04:33:04,640
PATIENTS THAT ARE ON

5209
04:33:04,640 --> 04:33:05,080
CHEMOTHERAPY.

5210
04:33:05,080 --> 04:33:06,840
THANK YOU VERY MUCH FOR YOUR

5211
04:33:06,840 --> 04:33:08,600
TALK.

5212
04:33:08,600 --> 04:33:16,440
OUR NEXT TALK IS FROM LIPING

5213
04:33:16,440 --> 04:33:23,280
ZHAO.

5214
04:33:23,280 --> 04:33:24,840
>> THANK YOU FOR YOUR

5215
04:33:24,840 --> 04:33:25,680
INTRODUCTION.

5216
04:33:25,680 --> 04:33:27,040
HIHI, EVERYONE.

5217
04:33:27,040 --> 04:33:28,680
I WOULD LIKE TO THANK THE

5218
04:33:28,680 --> 04:33:29,800
ORGANIZERS FOR THE OPPORTUNITY

5219
04:33:29,800 --> 04:33:30,520
TO SPEAK HERE.

5220
04:33:30,520 --> 04:33:33,920
I'M GOING TO DISCUSS HOW WE MAY

5221
04:33:33,920 --> 04:33:36,240
USE THE REFERENCE FREE AND THE

5222
04:33:36,240 --> 04:33:38,560
GUILT BASE MADE APPROACH TO

5223
04:33:38,560 --> 04:33:43,240
ANALYZE GENOME RESULT -- FOR

5224
04:33:43,240 --> 04:33:48,520
DISCOVERING PRO-BIOTIC BACTERIA

5225
04:33:48,520 --> 04:33:52,680
WITH ECOLOGICAL COMPETENCY.

5226
04:33:52,680 --> 04:33:56,440
THE COMPLEXITY AND DENSITY OF

5227
04:33:56,440 --> 04:33:57,960
MICROBES IN OUR GUTS IS SUCH

5228
04:33:57,960 --> 04:34:00,400
THAT IT CAN BE CALLED OUR --

5229
04:34:00,400 --> 04:34:01,440
JUNGLE.

5230
04:34:01,440 --> 04:34:03,840
TO UNDERSTAND THE ROLE OF SOME

5231
04:34:03,840 --> 04:34:09,040
COMPLEX -- EXISTENCE WE NEED TO

5232
04:34:09,040 --> 04:34:10,840
ADOPT THE REFERENCE OF THREE AND

5233
04:34:10,840 --> 04:34:12,320
THE APPROACH.

5234
04:34:12,320 --> 04:34:14,160
WHAT IS REFERENCE FREE.

5235
04:34:14,160 --> 04:34:19,440
IT MEANS THAT -- DATABASES TO

5236
04:34:19,440 --> 04:34:20,640
ANNOTATE.

5237
04:34:20,640 --> 04:34:23,240
BECAUSE A SUBSTANTIAL PART OF

5238
04:34:23,240 --> 04:34:27,840
OUR DATASET FROM NOVEL MEMBERS

5239
04:34:27,840 --> 04:34:30,800
-- AND THAT CANNOT BE PROPER

5240
04:34:30,800 --> 04:34:33,640
LEANN STATED.

5241
04:34:33,640 --> 04:34:35,920
VERY OFTEN WILL BE DISCARDED IN

5242
04:34:35,920 --> 04:34:37,840
THE DOWNSTREAM ANALYSIS.

5243
04:34:37,840 --> 04:34:41,200
IF YOU DO DATABASE -- YOU WILL

5244
04:34:41,200 --> 04:34:43,920
ONLY STUDY THE PART OF THE DATA

5245
04:34:43,920 --> 04:34:45,920
THAT HAS BEEN LOOKED AT BY OTHER

5246
04:34:45,920 --> 04:34:46,840
PEOPLE BEFORE.

5247
04:34:46,840 --> 04:34:49,360
TO OVERCOME THIS LIMITATION WE

5248
04:34:49,360 --> 04:34:55,840
SHOULD DO A NOVEL ASSEMBLY.

5249
04:34:55,840 --> 04:34:59,560
WHICH CAN THEM EXAMINE THE

5250
04:34:59,560 --> 04:35:01,240
BEHAVIOR AND ASSESS THEIR

5251
04:35:01,240 --> 04:35:04,280
CORRELATIONS.

5252
04:35:04,280 --> 04:35:11,000
WHAT IS GUILD?

5253
04:35:11,000 --> 04:35:12,800
MEMBERS FROM DIFFERENT SPECIES

5254
04:35:12,800 --> 04:35:15,840
WORK TOGETHER AS A COHERE

5255
04:35:15,840 --> 04:35:18,600
APARTMENT FUNCTION CALLED GUILD.

5256
04:35:18,600 --> 04:35:20,240
MEMBERS STRIVE OR DECLINE

5257
04:35:20,240 --> 04:35:24,360
TOGETHER.

5258
04:35:24,360 --> 04:35:28,840
BACK IN 2015 WE SHOWED THAT --

5259
04:35:28,840 --> 04:35:30,440
BACTERIA WAS RESPONSIBLE AS

5260
04:35:30,440 --> 04:35:33,440
GUILD AND NOT AS TEXTILE.

5261
04:35:33,440 --> 04:35:37,840
SOME VIEWED -- THE RESEARCH --

5262
04:35:37,840 --> 04:35:40,600
SOME ARE NEGATIVELY ASSOCIATE

5263
04:35:40,600 --> 04:35:45,040
AND OTHERS SHOWED NO

5264
04:35:45,040 --> 04:35:51,640
ASSOCIATIONS.

5265
04:35:51,640 --> 04:35:56,040
HOW CAN WE IDENTIFY GUILD WHICH

5266
04:35:56,040 --> 04:35:58,360
PLAICES IMPORTANT ROLES.

5267
04:35:58,360 --> 04:36:01,840
OUR WORKING HYPOTHESIS IS THAT A

5268
04:36:01,840 --> 04:36:04,680
DIFFERENT BACTERIA -- WHICH

5269
04:36:04,680 --> 04:36:08,240
PROVIDES ESSENTIAL FUNCTIONS TO

5270
04:36:08,240 --> 04:36:10,520
THE HOST ITS MEMBERS WILL NEED

5271
04:36:10,520 --> 04:36:13,800
TO KEEP A ROBUST ECOLOGICAL

5272
04:36:13,800 --> 04:36:18,400
RELATIONSHIP WITH EACH OTHER.

5273
04:36:18,400 --> 04:36:20,640
SO ONE STRATEGY FOR TESTING THIS

5274
04:36:20,640 --> 04:36:23,640
IS LOOKING FOR GENOME PAIRS

5275
04:36:23,640 --> 04:36:26,520
WHICH CAN KEEP STABLE ECOLOGICAL

5276
04:36:26,520 --> 04:36:32,120
ACCENT -- BY PROFOUND CHANGES.

5277
04:36:32,120 --> 04:36:35,120
WE DECIDE TO TEST THIS

5278
04:36:35,120 --> 04:36:40,040
HYPOTHESIS BY USING HIGH FIBER

5279
04:36:40,040 --> 04:36:44,520
-- -- AND IDENTIFY STABLE GENOME

5280
04:36:44,520 --> 04:36:47,080
PAIRS AS BACKBONE OF ESSENTIAL

5281
04:36:47,080 --> 04:36:47,600
GUILD.

5282
04:36:47,600 --> 04:36:50,440
IN THIS PUBLISHED CLINICAL TRIAL

5283
04:36:50,440 --> 04:36:53,120
ON TYPE II DIABETES THE

5284
04:36:53,120 --> 04:36:54,760
RANDOMIZED CONTROL DESIGN AND

5285
04:36:54,760 --> 04:36:59,480
THE TRANSPLANTATION -- FROM THE

5286
04:36:59,480 --> 04:37:01,600
SAME PATIENT DEMONSTRATED A

5287
04:37:01,600 --> 04:37:04,560
CAUSAL ROLE OF HIGH FIBER

5288
04:37:04,560 --> 04:37:07,080
ENRICHED -- PRODUCING BACTERIA

5289
04:37:07,080 --> 04:37:11,800
IN SUPPRESSING PATHOGENS -- --

5290
04:37:11,800 --> 04:37:16,600
SO WE DID ANOTHER LARGER SCALE

5291
04:37:16,600 --> 04:37:18,040
RANDOMIZED CONTROLLED TRIAL

5292
04:37:18,040 --> 04:37:20,360
WHICH HAD A ONE-YEAR --

5293
04:37:20,360 --> 04:37:22,440
FOLLOW-UP ON PATIENTS AFTER

5294
04:37:22,440 --> 04:37:24,960
THREE MONTHS HIGH FIBER

5295
04:37:24,960 --> 04:37:27,720
INTERVENTION.

5296
04:37:27,720 --> 04:37:31,840
BASELINE M0.

5297
04:37:31,840 --> 04:37:35,680
AND ONE YEAR FOLLOW-UP AFTER THE

5298
04:37:35,680 --> 04:37:36,800
HYPER INTERVENTION.

5299
04:37:36,800 --> 04:37:40,760
WE DID A MEDICAL CHECK UP.

5300
04:37:40,760 --> 04:37:46,080
WE ASSEMBLED 1845 HIGH QUALITY

5301
04:37:46,080 --> 04:37:49,720
-- BACTERIA GENOMES FROM THE

5302
04:37:49,720 --> 04:37:50,440
DATASET.

5303
04:37:50,440 --> 04:37:52,840
THESE GENOMES ACCOUNTED FOR 70%

5304
04:37:52,840 --> 04:37:55,040
OF THE TOTAL.

5305
04:37:55,040 --> 04:37:58,600
THIS MEANS THAT OUR -- ARE

5306
04:37:58,600 --> 04:38:11,040
DOMINATED BY BACTERIA.

5307
04:38:11,040 --> 04:38:17,480
ANONE YEAR AFTER THE -- STOPPED
--

5308
04:38:17,480 --> 04:38:19,400
NO DIFFERENCE FROM THE CONTROL

5309
04:38:19,400 --> 04:38:23,280
AND DISEASE ALSO CAME BACK.

5310
04:38:23,280 --> 04:38:29,600
SO AMONG THE 1845 GENOMES WE

5311
04:38:29,600 --> 04:38:30,520
SELECTED 447 BECAUSE THEY WERE

5312
04:38:30,520 --> 04:38:42,080
SHARED BY MORE THAN 75%.

5313
04:38:42,080 --> 04:38:47,800
-- -- OUT OF MORE THAN 100,000

5314
04:38:47,800 --> 04:38:51,080
POSSIBLE GENOME PAIRS MORE THAN

5315
04:38:51,080 --> 04:38:54,240
92% HAD -- AT THE END OF THE

5316
04:38:54,240 --> 04:38:55,560
THREE TIME POINTS.

5317
04:38:55,560 --> 04:38:57,440
INDICATING THAT IT'S A RARE

5318
04:38:57,440 --> 04:38:59,200
EVENTS FOR TWO GENOMES TO

5319
04:38:59,200 --> 04:39:02,640
ESTABLISH THE ECOLOGICAL

5320
04:39:02,640 --> 04:39:05,880
RELATIONSHIP.

5321
04:39:05,880 --> 04:39:10,480
635 PAIRS INVOLVING 141 GENOMES

5322
04:39:10,480 --> 04:39:11,960
WAS SELECTED BECAUSE THEY

5323
04:39:11,960 --> 04:39:14,440
CAPTURED THE SAME ECOLOGICAL

5324
04:39:14,440 --> 04:39:17,640
INTERACTION EITHER ALWAYS -- OR

5325
04:39:17,640 --> 04:39:20,200
ALWAYS -- CORRELATED ACROSS ALL

5326
04:39:20,200 --> 04:39:25,440
THE THREE TIME POINTS.

5327
04:39:25,440 --> 04:39:28,040
THESE 141 GENOMES WERE CLUSTERED

5328
04:39:28,040 --> 04:39:30,760
INTO TWO CUBES.

5329
04:39:30,760 --> 04:39:34,120
BASED ON THE STABLE INJECTIONS.

5330
04:39:34,120 --> 04:39:38,640
THERE WERE ONLY -- CORRELATIONS

5331
04:39:38,640 --> 04:39:42,480
INDICATING A -- OF RELATIONSHIP.

5332
04:39:42,480 --> 04:39:44,760
INTERESTINGLY IN THE NETWORKS

5333
04:39:44,760 --> 04:39:48,240
THESE HAVE ONLY 8% OF THE TOTAL

5334
04:39:48,240 --> 04:39:51,800
GENOMES BUT MORE THAN 80% OF THE

5335
04:39:51,800 --> 04:39:53,160
TOTAL REACTIONS.

5336
04:39:53,160 --> 04:39:58,040
IF WE REMOVE THESE 141 GENOMES

5337
04:39:58,040 --> 04:40:01,520
THE WHOLE NETWORK WILL COLLAPSE.

5338
04:40:01,520 --> 04:40:05,840
THESE TWO GUILDS WORK AS THE

5339
04:40:05,840 --> 04:40:07,760
MOST IMPORTANT MODELS IN THE

5340
04:40:07,760 --> 04:40:10,600
NETWORK.

5341
04:40:10,600 --> 04:40:13,960
THEY ARE THE MOST STABLE

5342
04:40:13,960 --> 04:40:18,800
CONNECTED AND ALSO HIGHLY

5343
04:40:18,800 --> 04:40:19,240
CONNECTED.

5344
04:40:19,240 --> 04:40:21,960
THEY ARE THE BACKBONE OF THAT

5345
04:40:21,960 --> 04:40:23,920
ECOLOGICAL NETWORK.

5346
04:40:23,920 --> 04:40:27,320
FUNCTIONAL ANALYSIS SO THAT THE

5347
04:40:27,320 --> 04:40:34,840
50 GENOMES HARBORED -- -- -- AND

5348
04:40:34,840 --> 04:40:35,680
-- PRODUCTION.

5349
04:40:35,680 --> 04:40:40,440
8 THIS MEANS THAT -- MAY HAVE

5350
04:40:40,440 --> 04:40:43,040
ADAPTED -- TO HIGH FIBER

5351
04:40:43,040 --> 04:40:44,600
ENVIRONMENT.

5352
04:40:44,600 --> 04:40:47,880
INTERESTINGLY THE 91 GENOMES HAD

5353
04:40:47,880 --> 04:40:56,840
A MUCH MORE --ANT BUY ON THE

5354
04:40:56,840 --> 04:41:13,640
CALL RESISTANCE.

5355
04:41:13,640 --> 04:41:21,800
----- INCREASE ITS ABUNDANCE

5356
04:41:21,800 --> 04:41:24,840
FROM M0 TO M3 AND THEN DECREASED

5357
04:41:24,840 --> 04:41:31,000
FROM M3 TO M16.

5358
04:41:31,000 --> 04:41:35,280
THE TWO FORMED AND ACTED AS A

5359
04:41:35,280 --> 04:41:37,160
SEESAW LIKE STRUCTURE.

5360
04:41:37,160 --> 04:41:40,440
BASED ON THE ABUNDANCE OF THIS

5361
04:41:40,440 --> 04:41:45,480
141 GENOMES PREDICTED 41 OUT OF

5362
04:41:45,480 --> 04:41:49,480
43 -- -- -- INDICATING A

5363
04:41:49,480 --> 04:41:52,920
SIGNIFICANT ASSOCIATION OF AT

5364
04:41:52,920 --> 04:41:56,440
LEAST 141 GENOMES.

5365
04:41:56,440 --> 04:42:00,480
---NOW THE QUESTION IS IS THIS

5366
04:42:00,480 --> 04:42:02,120
SEESAW LIKE NETWORK UNIQUE TO

5367
04:42:02,120 --> 04:42:08,200
OUR STUDY COHORT AND -- OR IS IT

5368
04:42:08,200 --> 04:42:11,600
AN INHERENT ECOLOGICAL PATTERN.

5369
04:42:11,600 --> 04:42:15,240
WE FIRST TESTED -- THE NETWORK

5370
04:42:15,240 --> 04:42:17,320
THAT EXISTED IN AN INDEPENDENT

5371
04:42:17,320 --> 04:42:20,200
CASE CONTROL TYPE II DIABETES

5372
04:42:20,200 --> 04:42:20,840
STUDY.

5373
04:42:20,840 --> 04:42:25,920
WITH OUR 141 GENOMES AND

5374
04:42:25,920 --> 04:42:29,240
REFERENCES -- IN BOTH CASE AND

5375
04:42:29,240 --> 04:42:29,760
CONTROLLED GROUPS.

5376
04:42:29,760 --> 04:42:33,280
YOU CAN SEE A SIMILAR SEESAW

5377
04:42:33,280 --> 04:42:35,480
NETWORK WAS DETECTED IN BOTH

5378
04:42:35,480 --> 04:42:41,280
GROUPS.

5379
04:42:41,280 --> 04:42:43,280
MODERATE PREDICTION -- CASE

5380
04:42:43,280 --> 04:42:43,960
UNDER CONTROL.

5381
04:42:43,960 --> 04:42:47,800
THIS MEANS THAT THE TWO SEESAW

5382
04:42:47,800 --> 04:42:50,880
NETWORK ARE NOT INTRINSIC

5383
04:42:50,880 --> 04:42:52,200
STRUCTURE.

5384
04:42:52,200 --> 04:42:54,880
ALSO NOT THE DIET SPECIFIC.

5385
04:42:54,880 --> 04:42:57,360
WE THEN TESTED THE MODEL IN

5386
04:42:57,360 --> 04:43:02,640
OTHER DISEASES OTHER THAN TYPE

5387
04:43:02,640 --> 04:43:07,800
II DIABETES.

5388
04:43:07,800 --> 04:43:12,320
WE FOUND A SIMILAR NETWORK

5389
04:43:12,320 --> 04:43:13,560
STRUCTURE OF THREE DIFFERENT

5390
04:43:13,560 --> 04:43:20,440
TYPES OF DISEASES.

5391
04:43:20,440 --> 04:43:23,640
MACHINE LEARNING MODEL BASED ON

5392
04:43:23,640 --> 04:43:26,280
THE 141 GENOMES HAD AN

5393
04:43:26,280 --> 04:43:29,320
OUTSTANDING PREDICTION POWER.

5394
04:43:29,320 --> 04:43:33,560
SO FURTHER CONFIRM THE RELEVANCE

5395
04:43:33,560 --> 04:43:38,360
-- WE INCLUDED 8 MORE

5396
04:43:38,360 --> 04:43:40,800
INDEPENDENT METHODS FROM FIVE

5397
04:43:40,800 --> 04:43:44,240
OTHER DISEASES ACROSS DIFFERENT

5398
04:43:44,240 --> 04:43:57,240
ETHNICITIES AND GEOGRAPHIES.

5399
04:43:57,240 --> 04:44:00,880
THE MACHINE LEARNING MODEL HAD A

5400
04:44:00,880 --> 04:44:05,640
-- POWER FOR -- ---IN ALL OF

5401
04:44:05,640 --> 04:44:07,640
THESE CASES.

5402
04:44:07,640 --> 04:44:08,760
SO THESE RESULTS SUGGEST THAT

5403
04:44:08,760 --> 04:44:11,720
THE TWO COMPETING VIEWS

5404
04:44:11,720 --> 04:44:13,920
ORGANIZED AS THE SEESAW LIKE

5405
04:44:13,920 --> 04:44:16,240
NETWORK ARE POSSIBLE --

5406
04:44:16,240 --> 04:44:19,000
STRUCTURE OF THE -- HUMAN .

5407
04:44:19,000 --> 04:44:22,080
AS WE KNOW -- FIBER INTAKE WAS

5408
04:44:22,080 --> 04:44:25,040
MUCH HIGHER AND ONLY REDUCED

5409
04:44:25,040 --> 04:44:27,560
SIGNIFICANTLY IN THE PAST 160

5410
04:44:27,560 --> 04:44:28,240
YEARS.

5411
04:44:28,240 --> 04:44:30,880
HIGH FIBER INTAKE MAY HAVE

5412
04:44:30,880 --> 04:44:33,440
LATITUDE FORMATION OF THIS

5413
04:44:33,440 --> 04:44:36,280
SEESAW FORMATION.

5414
04:44:36,280 --> 04:44:37,960
GENOMES MAY HAVE BEEN

5415
04:44:37,960 --> 04:44:39,440
TRANSMITTED OVER MILLIONS OF

5416
04:44:39,440 --> 04:44:45,840
YEARS FROM OUR COMMON ANCESTORS.

5417
04:44:45,840 --> 04:44:49,760
THEY MAY WORK AS A HIGH FIBER

5418
04:44:49,760 --> 04:44:52,720
SELECTIVE AND EVOLUTIONARY --

5419
04:44:52,720 --> 04:44:58,200
SUCH A SEESAW NETWORK MAY

5420
04:44:58,200 --> 04:45:00,960
AGGRAVATE VARIOUS CONDITIONS

5421
04:45:00,960 --> 04:45:02,640
DEPENDING ON THE BALANCE.

5422
04:45:02,640 --> 04:45:05,040
FROM ECOLOGICAL PERSPECTIVE NOT

5423
04:45:05,040 --> 04:45:08,240
ALL MEMBERS ARE EQUALLY

5424
04:45:08,240 --> 04:45:10,240
IMPORTANT FOR THE EXISTENCE.

5425
04:45:10,240 --> 04:45:16,400
FOR EXAMPLE -- AT A -- FOR THE

5426
04:45:16,400 --> 04:45:17,360
RAINFOREST.

5427
04:45:17,360 --> 04:45:19,920
IF YOU LOSE THE -- YOU MAY LOSE

5428
04:45:19,920 --> 04:45:21,800
EVERYTHING.

5429
04:45:21,800 --> 04:45:24,440
SO FOUNDATION SPECIES IS

5430
04:45:24,440 --> 04:45:27,240
DIFFERENT FROM CASE STONE

5431
04:45:27,240 --> 04:45:27,760
SPECIES.

5432
04:45:27,760 --> 04:45:29,640
IT'S IMPORTANT TO THE EXISTENCE.

5433
04:45:29,640 --> 04:45:31,240
FOUNDATION SPECIES IS IMPORTANT

5434
04:45:31,240 --> 04:45:41,200
TO THE -- ECOSYSTEM.

5435
04:45:41,200 --> 04:45:44,840
SINCE -- ---FROM MANY DIFFERENT

5436
04:45:44,840 --> 04:45:46,840
SPECIES AND WORK TOGETHER AS A

5437
04:45:46,840 --> 04:45:50,040
GUILD WE PERMEATE AS FOUNDATION

5438
04:45:50,040 --> 04:45:50,480
GUILD.

5439
04:45:50,480 --> 04:45:53,760
ITS COMPETING GUILD MAY INDUCE

5440
04:45:53,760 --> 04:45:56,720
OR AGGRAVATE DISEASES SO IT CAN

5441
04:45:56,720 --> 04:46:00,920
BE TERMED THE -- ---FOUNDATION

5442
04:46:00,920 --> 04:46:04,800
GUILD BACTERIA ARE OUR NATURAL

5443
04:46:04,800 --> 04:46:06,520
PRO-BIOTICS.

5444
04:46:06,520 --> 04:46:10,600
YOU MAY NOT -- ---OF THE

5445
04:46:10,600 --> 04:46:11,040
BACTERIA.

5446
04:46:11,040 --> 04:46:13,480
YOU ONLY NEED A MUTATION OF

5447
04:46:13,480 --> 04:46:16,000
SUPPORT.

5448
04:46:16,000 --> 04:46:22,280
MAKE IT DOMINANT.

5449
04:46:22,280 --> 04:46:23,880
>> YOU HAVE TWO MINUTES.

5450
04:46:23,880 --> 04:46:24,160
>> OKAY.

5451
04:46:24,160 --> 04:46:25,160
THANK YOU.

5452
04:46:25,160 --> 04:46:27,040
>> OUR DATA SHOWS THAT SOME

5453
04:46:27,040 --> 04:46:30,680
PATIENTS SUCH AS THE -- COHORTS

5454
04:46:30,680 --> 04:46:32,880
ONE MAY STILL HAVE THEIR OWN

5455
04:46:32,880 --> 04:46:34,880
FOUNDATION GUILD BACTERIA BUT AT

5456
04:46:34,880 --> 04:46:38,800
A LOWER ABUNDANCE POSSIBLY DUE

5457
04:46:38,800 --> 04:46:42,400
TO LONG-TERM DEFICIENCY.

5458
04:46:42,400 --> 04:46:48,640
PRO VOWIN -- PROVIDING
NUTRITIONAL

5459
04:46:48,640 --> 04:46:52,040
SUPPORT.

5460
04:46:52,040 --> 04:46:56,640
-- -- WE DEVELOPED THE FORMULA

5461
04:46:56,640 --> 04:46:59,760
WHICH HAS BEEN GIVEN -- ---BY

5462
04:46:59,760 --> 04:47:02,280
THE FDA FOR PATIENTS WHO HAVE

5463
04:47:02,280 --> 04:47:04,640
THEIR OWN FOUNDATION GUILD.

5464
04:47:04,640 --> 04:47:10,080
THIS FORMULA MAY HELP RECOVER --

5465
04:47:10,080 --> 04:47:13,520
---WE ARE CONDUCTING A TRIAL FOR

5466
04:47:13,520 --> 04:47:18,160
COVID-19 AND -- ---ON OTHER

5467
04:47:18,160 --> 04:47:20,000
PATIENTS INCLUDING MULTIPLE

5468
04:47:20,000 --> 04:47:22,200
SCLEROSIS AND PARKINSON DISEASES

5469
04:47:22,200 --> 04:47:24,480
AND CANCER CHEMOTHERAPY.

5470
04:47:24,480 --> 04:47:27,440
IN OUR RECENT CASE STUDY SHOWED

5471
04:47:27,440 --> 04:47:32,640
THAT -- -- BACTERIA -- -- --

5472
04:47:32,640 --> 04:47:35,440
SYMPTOMS IN LONG COVID OF

5473
04:47:35,440 --> 04:47:36,040
PATIENTS.

5474
04:47:36,040 --> 04:47:38,280
WHILE OTHER PATIENTS SUCH AS THE

5475
04:47:38,280 --> 04:47:40,360
SECOND -- COHORT HERE MAY HAVE

5476
04:47:40,360 --> 04:47:44,200
LOST MOST MEMBERS OF THEIR --

5477
04:47:44,200 --> 04:47:46,960
FOUNDATION GUILD THE SEESAW LIKE

5478
04:47:46,960 --> 04:47:49,000
NETWORK MAY NO LONGER HOLD THE

5479
04:47:49,000 --> 04:47:51,160
EFFECTS.

5480
04:47:51,160 --> 04:47:54,960
THE PATIENTS -- -- CANNOT

5481
04:47:54,960 --> 04:47:57,800
---RESTORE A HEALTHY STRUCTURE.

5482
04:47:57,800 --> 04:47:59,600
SO FOR PATIENTS WHO HAVE LOST

5483
04:47:59,600 --> 04:48:02,240
THEIR OWN -- GUILD WE CAN

5484
04:48:02,240 --> 04:48:04,320
IDENTIFY AND ISOLATE BACTERIA

5485
04:48:04,320 --> 04:48:07,280
FROM HEALTHY DONORS FOR

5486
04:48:07,280 --> 04:48:10,160
DEVELOPING PRECISION PRO-BIOTIC

5487
04:48:10,160 --> 04:48:11,280
THERAPY.

5488
04:48:11,280 --> 04:48:13,640
LIVE CULTURES WHICH ARE

5489
04:48:13,640 --> 04:48:16,120
CORRESPONDING TO THE GENOMES.

5490
04:48:16,120 --> 04:48:19,120
THE BACTERIA HAS THE ECOLOGICAL

5491
04:48:19,120 --> 04:48:23,760
-- FOR -- -- THEY ARE ALSO

5492
04:48:23,760 --> 04:48:25,440
ECOLOGICAL COMPATIBLE BECAUSE

5493
04:48:25,440 --> 04:48:29,320
THEY ARE -- SO IF YOU APPLY

5494
04:48:29,320 --> 04:48:29,760
THEM.

5495
04:48:29,760 --> 04:48:33,840
WE CAN ALSO PROVIDE APPROPRIATE

5496
04:48:33,840 --> 04:48:35,960
CARBOHYDRATES AS THE ENERGY

5497
04:48:35,960 --> 04:48:39,520
INPUT TO HELP FOUNDATION

5498
04:48:39,520 --> 04:48:41,120
BACTERIA RECOVER AND MAINTAIN

5499
04:48:41,120 --> 04:48:43,640
DOMINANCE.

5500
04:48:43,640 --> 04:48:46,280
SO WITH THAT I WOULD LIKE TO

5501
04:48:46,280 --> 04:48:47,440
FINISH WITH OF ACKNOWLEDGMENT

5502
04:48:47,440 --> 04:48:49,960
AND LOOKING FORWARD TO QUESTIONS

5503
04:48:49,960 --> 04:48:51,160
DURING OUR PANEL DISCUSSION.

5504
04:48:51,160 --> 04:48:52,920
THANK YOU.

5505
04:48:52,920 --> 04:48:55,040
>> THANK YOU VERY MUCH.

5506
04:48:55,040 --> 04:48:56,880
REALLY CONGRATULATE YOU ON

5507
04:48:56,880 --> 04:48:58,800
CLARIFYING THE CONCEPT OF

5508
04:48:58,800 --> 04:49:01,120
REFERENCE AND FREE AND GUILD

5509
04:49:01,120 --> 04:49:05,040
BASE APPROACHES FOR DISCOVERING

5510
04:49:05,040 --> 04:49:08,360
NOVEL PRO-BIOTIC BACTERIA.

5511
04:49:08,360 --> 04:49:11,240
WE'LL CONTINUE WITH DR. ANDREW

5512
04:49:11,240 --> 04:49:13,560
GOOD MAN TO WRAP UP THE

5513
04:49:13,560 --> 04:49:14,520
AFTERNOON.

5514
04:49:14,520 --> 04:49:17,640
THE MICROBIOME CONTRIBUTION TO

5515
04:49:17,640 --> 04:49:21,120
DRUG METABOLISM.

5516
04:49:21,120 --> 04:49:21,440
>> GREAT.

5517
04:49:21,440 --> 04:49:21,960
HI, EVERYONE.

5518
04:49:21,960 --> 04:49:24,280
THANK YOU FOR THE CHANCE TO

5519
04:49:24,280 --> 04:49:25,760
PARTICIPATE IN THIS WORKSHOP AND

5520
04:49:25,760 --> 04:49:28,360
TELL YOU A BIT ABOUT THE WORK

5521
04:49:28,360 --> 04:49:32,640
GOING ON IN MY LAB.

5522
04:49:32,640 --> 04:49:34,440
AND I'M GOING TO START AT THE

5523
04:49:34,440 --> 04:49:35,960
END WITH THE ACKNOWLEDGMENT.

5524
04:49:35,960 --> 04:49:38,040
I'M GOING TO TELL YOU ABOUT THE

5525
04:49:38,040 --> 04:49:40,040
WORK FROM A TEAM OF PEOPLE IN MY

5526
04:49:40,040 --> 04:49:43,040
LAB INITIALLY LED BY TWO

5527
04:49:43,040 --> 04:49:46,240
TALENTED FORMER POSTDOCS -- AND

5528
04:49:46,240 --> 04:49:49,240
NOW CURRENTLY BEING LED BY

5529
04:49:49,240 --> 04:49:52,280
ANDREW -- A GRADUATE STUDENT IN

5530
04:49:52,280 --> 04:49:54,440
THE LAB

5531
04:49:54,440 --> 04:49:56,040
>> YOU NEED TO GO TO

5532
04:49:56,040 --> 04:49:57,720
PRESENTATION MODE, PLEASE.

5533
04:49:57,720 --> 04:49:59,080
>> I'M IN PRESENTATION MODE.

5534
04:49:59,080 --> 04:50:02,280
>> JUST GO AHEAD -- GO AHEAD AND

5535
04:50:02,280 --> 04:50:05,840
HIT THE SLIDE SHOW ICON AT THE

5536
04:50:05,840 --> 04:50:07,240
BOTTOM OF YOUR SLIDES.

5537
04:50:07,240 --> 04:50:09,800
WE'RE SEEING YOUR SLIDES WITH

5538
04:50:09,800 --> 04:50:12,840
ALL OF THEM DOWN THE LEFT SLIDE.

5539
04:50:12,840 --> 04:50:14,640
>> I'M SORRY ABOUT THAT

5540
04:50:14,640 --> 04:50:16,920
>> NO WORRIES.

5541
04:50:16,920 --> 04:50:20,160
OR YOU MIGHT NEED TO SWAP

5542
04:50:20,160 --> 04:50:20,920
MONITORS.

5543
04:50:20,920 --> 04:50:22,240
WE'LL LET YOU BRING THAT BACK

5544
04:50:22,240 --> 04:50:31,000
UP.

5545
04:50:31,000 --> 04:50:32,880
>> DO YOU WANT TO TRY SHARING

5546
04:50:32,880 --> 04:50:35,640
AGAIN AND IF YOU HAVE ISSUES --

5547
04:50:35,640 --> 04:50:37,960
AND THEN COME DOWN TO THE BOTTOM

5548
04:50:37,960 --> 04:50:39,640
AND HIT YOUR SLIDE SHOW AND YOU

5549
04:50:39,640 --> 04:50:40,880
SHOULD BE FINE

5550
04:50:40,880 --> 04:50:43,320
>> WHAT DO YOU SEE NOW?

5551
04:50:43,320 --> 04:50:45,440
>> WE'RE NOT IN SLIDE SHOW MODE

5552
04:50:45,440 --> 04:50:45,840
YET.

5553
04:50:45,840 --> 04:50:47,960
CAN YOU ROLL YOUR CURSOR DOWN TO

5554
04:50:47,960 --> 04:50:50,400
THE BOTTOM AND HIT YOUR SLIDE

5555
04:50:50,400 --> 04:50:51,720
SHOW MODE?

5556
04:50:51,720 --> 04:50:54,480
>> I'M IN SLIDE SHOW ON MY

5557
04:50:54,480 --> 04:50:55,320
COMPUTER.

5558
04:50:55,320 --> 04:50:55,600
>> OKAY.

5559
04:50:55,600 --> 04:50:57,320
DAN IS GOING TO TAKE OVER AND

5560
04:50:57,320 --> 04:50:59,520
SHARE SLIDES ON YOUR BEHALF.

5561
04:50:59,520 --> 04:51:08,840
CAN YOU CUE DAN FOR DAN.

5562
04:51:08,840 --> 04:51:09,040
>> --

5563
04:51:09,040 --> 04:51:10,760
>> THIS IS DAN SHARING ON BEHALF

5564
04:51:10,760 --> 04:51:12,280
OF DR. GOOD MAN.

5565
04:51:12,280 --> 04:51:14,640
CAN YOU GO TO THE NEXT SLIDE,

5566
04:51:14,640 --> 04:51:15,240
PLEASE.

5567
04:51:15,240 --> 04:51:16,760
>> SO YOU CAN GO TO THE NEXT

5568
04:51:16,760 --> 04:51:17,440
SLIDE.

5569
04:51:17,440 --> 04:51:19,600
THANK YOU.

5570
04:51:19,600 --> 04:51:21,720
>> SO WE HAVE BEEN INTERESTED

5571
04:51:21,720 --> 04:51:24,360
FOR A LONG TIME IN USING MEDICAL

5572
04:51:24,360 --> 04:51:28,440
DRUGS AS CHEMICAL PROBES TO

5573
04:51:28,440 --> 04:51:31,440
UNDERSTAND THE MICROBIOME AND

5574
04:51:31,440 --> 04:51:33,200
THIS INTEREST WAS INSPIRED BY

5575
04:51:33,200 --> 04:51:35,440
THE HISTORY OF HOW WE LEARNED

5576
04:51:35,440 --> 04:51:36,240
ABOUT THE LIVER.

5577
04:51:36,240 --> 04:51:39,600
SO WE'VE KNOWN FOR APPRECIATED

5578
04:51:39,600 --> 04:51:42,640
THE THE POWER OF THE LIVER FOR

5579
04:51:42,640 --> 04:51:44,800
CENTURIES.

5580
04:51:44,800 --> 04:51:46,840
AND MUCH OF WHAT WE KNOW NOW

5581
04:51:46,840 --> 04:51:49,520
ABOUT LIVER COMES FROM OUR STUDY

5582
04:51:49,520 --> 04:51:52,960
OF HOW MEDICAL DRUGS ARE

5583
04:51:52,960 --> 04:51:54,680
METABOLIZED BY THIS ORGAN.

5584
04:51:54,680 --> 04:51:56,680
AND ALONG THE WAY WE'VE LEARNED

5585
04:51:56,680 --> 04:52:00,040
HOW TO IMPROVE THE SAFETY AND

5586
04:52:00,040 --> 04:52:01,600
EFFICACY OF MEDICAL DRUGS BUT

5587
04:52:01,600 --> 04:52:03,040
ALSO HAVE LEARNED THAT MANY OF

5588
04:52:03,040 --> 04:52:06,000
THE PROCESSES THAT DRUGS THAT

5589
04:52:06,000 --> 04:52:08,120
THE LIVER CARRIES OUT ON MEDICAL

5590
04:52:08,120 --> 04:52:10,440
DRUGS ALSO ARE PART OF THE

5591
04:52:10,440 --> 04:52:13,160
NORMAL PHYSIOLOGY OF THIS ORGAN

5592
04:52:13,160 --> 04:52:14,960
AND WE REASON THAT SAME

5593
04:52:14,960 --> 04:52:17,200
APPROACHES COULD TEACH US ABOUT

5594
04:52:17,200 --> 04:52:18,400
THE MICROBIOME.

5595
04:52:18,400 --> 04:52:21,120
SO NEXT SLIDE.

5596
04:52:21,120 --> 04:52:24,320
SO WHEN I WAS MENTIONING SAFETY

5597
04:52:24,320 --> 04:52:27,040
AND EFFICACY IT'S USEFUL TO

5598
04:52:27,040 --> 04:52:28,240
START WITH THE GUIDE ABS FROM

5599
04:52:28,240 --> 04:52:31,560
THE FDA WHICH IS NOT ONLY DRUGS

5600
04:52:31,560 --> 04:52:33,880
BUT ALSO THEIR METABOLITES CAN

5601
04:52:33,880 --> 04:52:37,000
PLAY A ROLE IN SAFETY OF DRUGS

5602
04:52:37,000 --> 04:52:41,240
AND THE CURRENT GUIDANCE IS IF A

5603
04:52:41,240 --> 04:52:43,200
DRUG METABOLITE EACHS 10% OF THE

5604
04:52:43,200 --> 04:52:45,440
TOTAL EXPOSER THAT IS ENOUGH TO

5605
04:52:45,440 --> 04:52:47,880
MONITOR FOR POTENTIAL SAFETY

5606
04:52:47,880 --> 04:52:48,800
CONCERNS.

5607
04:52:48,800 --> 04:52:50,800
SO WE'RE INTERESTED IN BOTH

5608
04:52:50,800 --> 04:52:55,040
DRUGS AND IN THEIR METABOLITES.

5609
04:52:55,040 --> 04:52:57,040
SO WE'VE LEARNED QUITE A BIT

5610
04:52:57,040 --> 04:52:59,160
TODAY ABOUT HUMAN AND ANIMAL

5611
04:52:59,160 --> 04:53:01,840
STUDIES OF THE MICROBIOME.

5612
04:53:01,840 --> 04:53:04,000
SO THIS STATEMENT AT THE TOP

5613
04:53:04,000 --> 04:53:05,840
WILL NOT BE CONTROVERSIAL TO

5614
04:53:05,840 --> 04:53:07,040
THIS AUDIENCE.

5615
04:53:07,040 --> 04:53:08,720
BUT WHAT I WOULD ARGUE IS THAT

5616
04:53:08,720 --> 04:53:11,080
AT THE VERY LEAST TYPICAL

5617
04:53:11,080 --> 04:53:12,840
PRECLINICAL ANIMAL STUDIES ARE

5618
04:53:12,840 --> 04:53:16,160
NOT DESIGNED TO MEASURE THE

5619
04:53:16,160 --> 04:53:17,240
MICROBIOME IMPACT.

5620
04:53:17,240 --> 04:53:20,880
AND ONE REASON IS HERE FROM THE

5621
04:53:20,880 --> 04:53:22,560
CONSORTIUM SHOWING THAT ALTHOUGH

5622
04:53:22,560 --> 04:53:26,160
AT THE BROAD LEVEL THE LEVEL

5623
04:53:26,160 --> 04:53:28,400
THAT IS CONSERVED BETWEEN HUMANS

5624
04:53:28,400 --> 04:53:30,600
AND PRECLINICAL MODEL SPECIES

5625
04:53:30,600 --> 04:53:33,040
ONCE YOU START LOOKING AT A GENE

5626
04:53:33,040 --> 04:53:37,360
CATALOG YOU CAN SEE THAT THE

5627
04:53:37,360 --> 04:53:39,480
OVERLAP IS -- GETS SMALLER AND

5628
04:53:39,480 --> 04:53:41,880
THAT IS HIGHLIGHTED IN THE

5629
04:53:41,880 --> 04:53:44,560
FIGURE ON THE RIGHT WHERE IN

5630
04:53:44,560 --> 04:53:46,440
PINK IS THE FRACTION OF THE

5631
04:53:46,440 --> 04:53:49,760
GENES IN THE META GENOME FROM

5632
04:53:49,760 --> 04:53:51,320
THESE DIFFERENT SPECIES THAT ARE

5633
04:53:51,320 --> 04:53:53,600
SHARED WITH HUMAN AND GRAY IS

5634
04:53:53,600 --> 04:53:55,200
THE FRACTION THAT IS NOT.

5635
04:53:55,200 --> 04:53:59,040
SO AGAIN WE'RE NOT CAPTURING THE

5636
04:53:59,040 --> 04:54:01,440
GENETIC REPERTOIRE BY LOOKING IN

5637
04:54:01,440 --> 04:54:03,440
TYPICAL PRECLINICAL ANIMAL

5638
04:54:03,440 --> 04:54:05,920
STUDIES OF DRUG METABOLISM.

5639
04:54:05,920 --> 04:54:11,800
7 SO OF COURSE DRUGS ARE ALSO

5640
04:54:11,800 --> 04:54:14,520
STUDIED IN HUMANS BEFORE THEY GO

5641
04:54:14,520 --> 04:54:17,200
TO MARKET AND ONE OF THE

5642
04:54:17,200 --> 04:54:19,720
IMPORTANT STAGES IS MASS BALANCE

5643
04:54:19,720 --> 04:54:21,840
STUDIES WHERE SMALL AMOUNTS OF

5644
04:54:21,840 --> 04:54:23,840
LABEL DRUGS ARE GIVEN TO A SET

5645
04:54:23,840 --> 04:54:27,120
OF USUALLY FOUR TO 8

5646
04:54:27,120 --> 04:54:28,200
INDIVIDUALS.

5647
04:54:28,200 --> 04:54:29,960
URINE AND FECES ARE COLLECTED

5648
04:54:29,960 --> 04:54:32,600
AND THEN THE LABEL IS QUANTIFIED

5649
04:54:32,600 --> 04:54:35,200
AND TYPICALLY AT LEAST 80% OF

5650
04:54:35,200 --> 04:54:37,960
THE LABELED COMPOUND IS

5651
04:54:37,960 --> 04:54:39,680
RECOVERED AND APPROACHES ARE

5652
04:54:39,680 --> 04:54:41,880
USED TO LOOK AT THE METABOLITES

5653
04:54:41,880 --> 04:54:43,560
THAT ARE PRODUCED.

5654
04:54:43,560 --> 04:54:45,800
BUT WHAT IS CLEAR IS THAT WHEN

5655
04:54:45,800 --> 04:54:48,480
WE ANY ABOUT THE MICROBIOME A

5656
04:54:48,480 --> 04:54:52,320
STUDY OF 4-6 INDIVIDUALS IS

5657
04:54:52,320 --> 04:54:54,200
UNLIKELY TO CAPTURE THE RANGE

5658
04:54:54,200 --> 04:54:56,280
THAT WE KNOW TO EXIST.

5659
04:54:56,280 --> 04:54:59,680
AND ALSO IN THIS DATA FROM AGAIN

5660
04:54:59,680 --> 04:55:01,880
FROM META HIT SHOWING THE

5661
04:55:01,880 --> 04:55:04,800
LARGEST CATEGORY OF GENES IN

5662
04:55:04,800 --> 04:55:06,800
THESE STUDIES ARE THOSE THAT ARE

5663
04:55:06,800 --> 04:55:09,240
FOUND IN LESS THAN ONE OUT OF

5664
04:55:09,240 --> 04:55:12,440
SIX INDIVIDUALS.

5665
04:55:12,440 --> 04:55:14,840
AND SO ALSO WHEN WE LOOK AT

5666
04:55:14,840 --> 04:55:17,640
URINE AND FECES THIS MAY NOT

5667
04:55:17,640 --> 04:55:20,640
TELL US WHERE IN THE BODY A DRUG

5668
04:55:20,640 --> 04:55:21,560
METABOLITE IS MADE.

5669
04:55:21,560 --> 04:55:25,000
SO DESPITE THE FACT THAT THESE

5670
04:55:25,000 --> 04:55:27,240
TYPICAL PRECLINICAL STUDIES ARE

5671
04:55:27,240 --> 04:55:30,040
DESIGNED TO ALMOST AVOID SEEING

5672
04:55:30,040 --> 04:55:35,720
MICRO BIOMEDIA DRUG METABOLISM

5673
04:55:35,720 --> 04:55:38,840
THE GUT IS STILL EMERGING AS A

5674
04:55:38,840 --> 04:55:40,360
SECOND ORGAN.

5675
04:55:40,360 --> 04:55:44,960
AND NEXT PANEL SHOWS SOME OF THE

5676
04:55:44,960 --> 04:55:46,240
MODIFICATIONS THAT HAVE BEEN

5677
04:55:46,240 --> 04:55:48,040
OBSERVED AND THE POINTS HERE IS

5678
04:55:48,040 --> 04:55:50,880
THAT THERE IS QUITE A DIVERSITY

5679
04:55:50,880 --> 04:55:53,080
OF METABOLIC REACTIONS THAT HAVE

5680
04:55:53,080 --> 04:55:55,520
BEEN ASSOCIATED WITH MICROBIAL

5681
04:55:55,520 --> 04:55:56,160
ACTIVITY.

5682
04:55:56,160 --> 04:55:58,720
THIS MAY BE BECAUSE THEY ARE

5683
04:55:58,720 --> 04:56:02,120
USING THESE DRUGS NOT JUST TO

5684
04:56:02,120 --> 04:56:05,800
ELIMINATE THEM FROM THE BODY AND

5685
04:56:05,800 --> 04:56:07,480
THEN ALSO THAT THE DRUGS THAT

5686
04:56:07,480 --> 04:56:10,640
HAVE BEEN ASSOCIATE WITH MICRO

5687
04:56:10,640 --> 04:56:13,520
BIOMEDIA AND METABOLISM SPAN

5688
04:56:13,520 --> 04:56:15,320
MANY DISEASE INDICATIONS

5689
04:56:15,320 --> 04:56:16,960
INCLUDING MOST OF THEM OUTSIDE

5690
04:56:16,960 --> 04:56:21,680
OF THE GUT.

5691
04:56:21,680 --> 04:56:25,480
SO I ALSO WANT TO COME BACK TO

5692
04:56:25,480 --> 04:56:28,840
THE THEME OF SHARED METABOLISM

5693
04:56:28,840 --> 04:56:30,800
BETWEEN THE GUT AND THE LIVER.

5694
04:56:30,800 --> 04:56:33,920
SO EVEN IF THE REACTION IS

5695
04:56:33,920 --> 04:56:35,160
IDENTICAL IT'S STILL IMPORTANT

5696
04:56:35,160 --> 04:56:37,200
TO UNDERSTAND WHERE IN THE BODY

5697
04:56:37,200 --> 04:56:39,080
THIS METABOLISM IS OCCURRING

5698
04:56:39,080 --> 04:56:40,640
BECAUSE ALL OF THE FACTORS ON

5699
04:56:40,640 --> 04:56:43,040
THIS SLIDE WILL HAVE A DIFFERENT

5700
04:56:43,040 --> 04:56:45,360
IMPACT ON DRUG METABOLISM.

5701
04:56:45,360 --> 04:56:47,240
DEPENDING ON WHETHER THE

5702
04:56:47,240 --> 04:56:48,400
MICROBIOME OR LIVE IS

5703
04:56:48,400 --> 04:56:52,120
RESPONSIBLE AND I'LL COME BACK

5704
04:56:52,120 --> 04:56:53,000
TO THIS.

5705
04:56:53,000 --> 04:56:55,280
THE QUESTIONS ARE BASIC.

5706
04:56:55,280 --> 04:56:57,520
MANY WOULD ARGUE THAT THESE

5707
04:56:57,520 --> 04:57:01,680
QUESTIONS * HAVE BEEN ADDRESSED

5708
04:57:01,680 --> 04:57:04,240
30-40 YEARS AGO AND WE STILL

5709
04:57:04,240 --> 04:57:05,200
DON'T HAVE THE ANSWERS WHEN WE

5710
04:57:05,200 --> 04:57:08,920
LOOK AT HOW THE MICROBIOME

5711
04:57:08,920 --> 04:57:11,040
METABOLIZES DRUGS SO WE SET OUT

5712
04:57:11,040 --> 04:57:12,680
TO GENERATE A PIPELINE THAT

5713
04:57:12,680 --> 04:57:14,240
WOULD ALLOW US TO MAP THE

5714
04:57:14,240 --> 04:57:17,440
CAPACITY OF HUMAN GUT MICROBES

5715
04:57:17,440 --> 04:57:19,640
TO METABOLIZE DRUGS WITH THE

5716
04:57:19,640 --> 04:57:21,640
GOAL OF ANSWERING THE QUESTIONS

5717
04:57:21,640 --> 04:57:23,360
ON THIS SLIDE AS WELL AS

5718
04:57:23,360 --> 04:57:26,000
IDENTIFYING KEY MICROBES THAT

5719
04:57:26,000 --> 04:57:27,720
MAY BE IMPORTANT FOR THESE

5720
04:57:27,720 --> 04:57:30,680
PROCESSES.

5721
04:57:30,680 --> 04:57:32,360
SO IN THE INTEREST OF TIME I

5722
04:57:32,360 --> 04:57:33,800
WON'T GO THROUGH THE DETAILS OF

5723
04:57:33,800 --> 04:57:35,680
THE METHOD BUT I'LL TELL YOU

5724
04:57:35,680 --> 04:57:39,240
THAT WE USED AN INVITRO POOLING

5725
04:57:39,240 --> 04:57:42,120
METHOD TO SURVEY THE CAPACITY OF

5726
04:57:42,120 --> 04:57:48,160
76 DIFFERENT GUT BACTERIA.

5727
04:57:48,160 --> 04:57:51,600
AND WE DID THIS BY COMBINING THE

5728
04:57:51,600 --> 04:57:54,560
DRUGS INTO POOLS AND THEN USING

5729
04:57:54,560 --> 04:57:57,600
MASS SPECTORMETRY TO QUAINT TIE

5730
04:57:57,600 --> 04:58:00,440
AND IDENTIFY THE METABOLITES IN

5731
04:58:00,440 --> 04:58:02,720
THE PRESENCE OF EACH OF THESE

5732
04:58:02,720 --> 04:58:04,240
GUT BACTERIA.

5733
04:58:04,240 --> 04:58:07,640
SO I'M SHOWING YOU HERE A HEAT

5734
04:58:07,640 --> 04:58:09,240
MAP OF THE DATA WHERE EACH

5735
04:58:09,240 --> 04:58:11,560
COLUMN IS ONE OF THE DRUGS THAT

5736
04:58:11,560 --> 04:58:13,440
WAS METABOLIZED BY ONE OF THE

5737
04:58:13,440 --> 04:58:16,120
SPECIES THAT WE HAD INCLUDED AND

5738
04:58:16,120 --> 04:58:17,840
EACH ROW REPRESENTS ONE OF THE

5739
04:58:17,840 --> 04:58:19,000
76 SPECIES.

5740
04:58:19,000 --> 04:58:21,440
THERE IS A FEW TAKE HOME HIGH

5741
04:58:21,440 --> 04:58:22,880
LEVEL MESSAGES THAT WE LEARNED

5742
04:58:22,880 --> 04:58:23,440
FROM THIS.

5743
04:58:23,440 --> 04:58:26,000
THE FIRST IS THAT FOR ABOUT

5744
04:58:26,000 --> 04:58:27,440
TWO-THIRDS OF THE DRUGS THAT WE

5745
04:58:27,440 --> 04:58:29,520
TESTED WE COULD FIND AT LEAST

5746
04:58:29,520 --> 04:58:33,120
ONE MICROBE THAT METABOLIZED THE

5747
04:58:33,120 --> 04:58:34,040
DRUG.

5748
04:58:34,040 --> 04:58:36,040
THE SECOND WAS THAT WHEN WE

5749
04:58:36,040 --> 04:58:39,640
CLUSTERED THE DATA RELATED

5750
04:58:39,640 --> 04:58:42,560
MICROBES CLUSTER TOGETHER

5751
04:58:42,560 --> 04:58:44,560
SUBJECTING THERE IS AN

5752
04:58:44,560 --> 04:58:47,560
UNDERLYING LOGIC AND THIRD,

5753
04:58:47,560 --> 04:58:49,880
THERE WERE EXAMPLES WHERE DRUGS

5754
04:58:49,880 --> 04:58:53,520
WITH CHEMICAL SIMILARITY WERE

5755
04:58:53,520 --> 04:58:55,320
METABOLIZED OR IGNORED BY THE

5756
04:58:55,320 --> 04:58:57,280
SAME MICROBES.

5757
04:58:57,280 --> 04:58:59,600
SUGGESTING A LANGUAGE OF WHAT WE

5758
04:58:59,600 --> 04:59:01,040
DON'T UNDERSTAND OF HOW FAR

5759
04:59:01,040 --> 04:59:02,800
THESE MICROBES ARE RECOGNIZING

5760
04:59:02,800 --> 04:59:04,920
THE DRUGS AND DECIDING WHAT TO

5761
04:59:04,920 --> 04:59:06,320
DO WITH THEM.

5762
04:59:06,320 --> 04:59:08,240
ALTHOUGH THESE PATTERNS AT THE

5763
04:59:08,240 --> 04:59:10,040
BROAD SENSE ONCE WE START

5764
04:59:10,040 --> 04:59:12,000
LOOKING AT MORE DETAIL THINGS

5765
04:59:12,000 --> 04:59:13,440
GET MORE COMPLICATED.

5766
04:59:13,440 --> 04:59:19,040
HERE IS ONE EXAMPLE -- IT IS

5767
04:59:19,040 --> 04:59:21,960
METABOLIZED MOST ACTIVELY.

5768
04:59:21,960 --> 04:59:26,040
YOU CAN SEE ALSO MANY OTHER

5769
04:59:26,040 --> 04:59:28,040
BACTERIA THAT DON'T METABOLIZE

5770
04:59:28,040 --> 04:59:29,440
THE DRUG.

5771
04:59:29,440 --> 04:59:33,040
SO WE AGAIN USE MASS

5772
04:59:33,040 --> 04:59:35,160
SPECTORMETRY TO DETERMINE WHICH

5773
04:59:35,160 --> 04:59:38,360
METABOLITE WAS BEING MADE.

5774
04:59:38,360 --> 04:59:42,440
AND NEXT -- WHAT WE FOUND IS BY

5775
04:59:42,440 --> 04:59:44,240
IDENTIFYING THE ACTUAL GENE

5776
04:59:44,240 --> 04:59:45,440
RESPONSIBLE FOR THIS ACTIVITY WE

5777
04:59:45,440 --> 04:59:47,080
HAD A BIOMARKER.

5778
04:59:47,080 --> 04:59:49,240
SO, IT'S NOT THE NAME OF THE

5779
04:59:49,240 --> 04:59:51,240
BACTERIA OR EVEN THE FUNCTIONAL

5780
04:59:51,240 --> 04:59:54,360
CLASS OF THE ENZYME THAT TELLS

5781
04:59:54,360 --> 04:59:57,560
US WHETHER OR NOT A -- DRUG --

5782
04:59:57,560 --> 04:59:59,520
IT REQUIRES FINDING THE

5783
04:59:59,520 --> 05:00:02,320
INDIVIDUAL ENZYME THAT IS

5784
05:00:02,320 --> 05:00:03,840
RESPONSIBLE.

5785
05:00:03,840 --> 05:00:07,240
ONCE WE KNOW WE THEN HAVE AN

5786
05:00:07,240 --> 05:00:09,840
INDICATOR THAT DISTINGUISHES THE

5787
05:00:09,840 --> 05:00:13,640
MOST ACTIVE STRAINS.

5788
05:00:13,640 --> 05:00:18,280
THIS GENE PREDICTS THE ACTIVITY

5789
05:00:18,280 --> 05:00:21,720
OF A COMPLETE HUMAN GUT

5790
05:00:21,720 --> 05:00:23,480
MICROBIOMES IN METABOLIZING THIS

5791
05:00:23,480 --> 05:00:24,440
DRUG.

5792
05:00:24,440 --> 05:00:27,080
SO IN MY LAST FEW MINUTES I WANT

5793
05:00:27,080 --> 05:00:30,040
TO TURN TO THIS SECOND POINT

5794
05:00:30,040 --> 05:00:31,960
WHICH IS THAT WHEN WE SAW THAT

5795
05:00:31,960 --> 05:00:35,040
THERE WERE SO MANY MICROBE

5796
05:00:35,040 --> 05:00:36,840
THAT'S COULD METABOLIZE THESE

5797
05:00:36,840 --> 05:00:38,840
DRUGS AND THAT TWO-THIRDS OF THE

5798
05:00:38,840 --> 05:00:41,400
DRUGS WERE METABOLIZED BY ONE

5799
05:00:41,400 --> 05:00:44,480
SPECIES WE STARTED TO THINK THAT

5800
05:00:44,480 --> 05:00:48,040
MAYBE SOME OF THE THAT HAD BEEN

5801
05:00:48,040 --> 05:00:49,680
ATTRIBUTED TO LIVER ACTIVITY MAY

5802
05:00:49,680 --> 05:00:52,840
BE DUE TO MICROBIOME ACTIVITY.

5803
05:00:52,840 --> 05:00:54,840
I'LL SHOW YOU ONE EXAMPLE WHICH

5804
05:00:54,840 --> 05:00:57,600
IS ANTI VIRAL DRUG.

5805
05:00:57,600 --> 05:01:02,000
IT'S METABOLIZED -- BY BOTH THE

5806
05:01:02,000 --> 05:01:03,880
LIVER AND THE THE MICROBIOME AND

5807
05:01:03,880 --> 05:01:06,440
THIS MATTERS BECAUSE THIS

5808
05:01:06,440 --> 05:01:09,520
METABOLITE CAN CONTRIBUTE TO A

5809
05:01:09,520 --> 05:01:11,720
DRUG DRUG INTERACTION THAT HASH

5810
05:01:11,720 --> 05:01:12,360
FATAL.

5811
05:01:12,360 --> 05:01:16,800
THE NATIVE SUB STRAIGHT AND THE

5812
05:01:16,800 --> 05:01:23,920
REASON IS THAT -- BVU INHIBITS

5813
05:01:23,920 --> 05:01:30,840
-- WHEN PEOPLE TAKE BRIVUDINE --

5814
05:01:30,840 --> 05:01:32,240
THEY SHOW ACCUMULATION.

5815
05:01:32,240 --> 05:01:37,200
BUT DRUGS THAT LOOK LIKE -- 80%

5816
05:01:37,200 --> 05:01:40,360
OF -- IS CLEARED.

5817
05:01:40,360 --> 05:01:43,760
SO INHIBITION CAUSES A FATAL

5818
05:01:43,760 --> 05:01:48,040
ACCUMULATION OF THIS CHEMO

5819
05:01:48,040 --> 05:01:49,680
THERAPEUTIC.

5820
05:01:49,680 --> 05:01:53,200
TO AGAIN IDENTIFY THE SPECIFIC

5821
05:01:53,200 --> 05:01:56,280
ENZYME THAT GUT MICROBES USE.

5822
05:01:56,280 --> 05:01:59,040
AND WHAT WAS USEFUL IS THAT WE

5823
05:01:59,040 --> 05:02:04,440
CAN COLONIZE GERMFREE MICE WITH

5824
05:02:04,440 --> 05:02:06,120
MUTANT STRAINS AND THEN MEASURE

5825
05:02:06,120 --> 05:02:09,040
THE TOXICITY OF THE DRUG AFTER

5826
05:02:09,040 --> 05:02:11,120
IN THE LIVER IN THE PRESENCE OF

5827
05:02:11,120 --> 05:02:25,040
THESE EYEWITNESSES O -- ISOGENIC
STRAINS.

5828
05:02:25,040 --> 05:02:27,320
AND SO YOU CAN SEE THE

5829
05:02:27,320 --> 05:02:30,400
SIGNIFICANT DIFFERENCE IN THE

5830
05:02:30,400 --> 05:02:32,040
ACCUMULATION DUE TO JUST A

5831
05:02:32,040 --> 05:02:35,840
SINGLE ENZYME IN THE GUT

5832
05:02:35,840 --> 05:02:37,520
MICROBES OF THESE MICE.

5833
05:02:37,520 --> 05:02:39,440
SO TAKING CAREFUL MEASUREMENTS

5834
05:02:39,440 --> 05:02:42,200
OF THE LEVELS OF DRUGS AND

5835
05:02:42,200 --> 05:02:43,880
METABOLITES IN EACH SECTION OF

5836
05:02:43,880 --> 05:02:45,640
THE GUT AS WELL AS OVER TIME

5837
05:02:45,640 --> 05:02:48,200
ALLOWS US TO BUILD MATHEMATICAL

5838
05:02:48,200 --> 05:02:50,320
MODELS TO DESCRIBE THIS PROCESS.

5839
05:02:50,320 --> 05:02:52,720
THE REASON FOR BUILDING THESE

5840
05:02:52,720 --> 05:02:54,960
MODELS IS TO QUANTIFY HOW MUCH

5841
05:02:54,960 --> 05:02:59,160
THE MICROBIOME IS CONTRIBUTING

5842
05:02:59,160 --> 05:03:01,240
AND THEN SECOND TO PREDICT HOW

5843
05:03:01,240 --> 05:03:04,560
DIFFERENT FACTORS SUCH AS IF MY

5844
05:03:04,560 --> 05:03:06,800
MICROBIOME IS MORE ACTIVE THAN

5845
05:03:06,800 --> 05:03:10,080
YOURS OR A DRUG SHOWS DELAYED

5846
05:03:10,080 --> 05:03:11,640
ABSORBS HOW THESE DIFFERENT

5847
05:03:11,640 --> 05:03:13,360
FACTORS MAY IMPACT THE

5848
05:03:13,360 --> 05:03:15,440
CONTRIBUTION OF THE MICROBIOME.

5849
05:03:15,440 --> 05:03:17,040
I WON'T GET INTO THE DETAILS.

5850
05:03:17,040 --> 05:03:19,800
IT'S A COMPARTMENTAL MODEL WHERE

5851
05:03:19,800 --> 05:03:22,240
WE USE OUR MEASUREMENTS IN THESE

5852
05:03:22,240 --> 05:03:27,040
MICE THAT VARY IN A SINGLE DRUG

5853
05:03:27,040 --> 05:03:29,840
METABOLIZING ENZYME TO PREDICT

5854
05:03:29,840 --> 05:03:33,240
NOT ONLY THE LEVELS OF

5855
05:03:33,240 --> 05:03:34,280
METABOLITES THAT ARE APPEARING

5856
05:03:34,280 --> 05:03:36,000
IN THE GUT BUT ALSO HOW MUCH OF

5857
05:03:36,000 --> 05:03:40,160
THAT IS ENDING UP IN THE SERUM

5858
05:03:40,160 --> 05:03:42,160
AND THESE CAN GET MORE

5859
05:03:42,160 --> 05:03:45,040
COMPLICATED -- AS SHOWN HERE AS

5860
05:03:45,040 --> 05:03:47,040
WELL AS MULTIPLE METABOLITES

5861
05:03:47,040 --> 05:03:49,640
WHICH I'M NOT GOING TO GET INTO

5862
05:03:49,640 --> 05:03:49,840
NOW

5863
05:03:49,840 --> 05:03:51,640
>> YOU HAVE ABOUT TWO MINUTES.

5864
05:03:51,640 --> 05:03:52,800
>> GREAT.

5865
05:03:52,800 --> 05:03:55,000
JUST THE TAKE HOME MESSAGE THIS

5866
05:03:55,000 --> 05:03:57,160
ALLOWS US TO PUT A NUMBER ON HOW

5867
05:03:57,160 --> 05:03:59,640
MUCH OF THE TOXIC DRUG

5868
05:03:59,640 --> 05:04:02,400
METABOLITE IS BEING PRODUCED.

5869
05:04:02,400 --> 05:04:05,720
AND WHAT THE MODEL TELLS US IS

5870
05:04:05,720 --> 05:04:08,040
ABOUT 70% OF METABOLITE IS

5871
05:04:08,040 --> 05:04:09,840
COMING FROM WHAT THE BACTERIA

5872
05:04:09,840 --> 05:04:10,480
ARE DOING.

5873
05:04:10,480 --> 05:04:12,720
AND THE NEXT SLIDE POINTS OUT

5874
05:04:12,720 --> 05:04:15,800
THAT THIS IS A DRUG THAT IS

5875
05:04:15,800 --> 05:04:18,000
FAIRLY WELL ABSORBED.

5876
05:04:18,000 --> 05:04:22,040
WE KNOW THE LIVER IS ABLE TO

5877
05:04:22,040 --> 05:04:24,200
CARRY OUT THIS AND LITTLE IS

5878
05:04:24,200 --> 05:04:26,280
FOUND IN FECES BECAUSE IT'S SO

5879
05:04:26,280 --> 05:04:27,800
READILY ABSORBED.

5880
05:04:27,800 --> 05:04:30,960
EVEN DRUGS WITH CHARACTERISTICS

5881
05:04:30,960 --> 05:04:33,240
CAN STILL HAVE A LARGE

5882
05:04:33,240 --> 05:04:34,640
MICROBIOME CONTRIBUTION.

5883
05:04:34,640 --> 05:04:36,680
SO IN THE LAST FEW SLIDES I'LL

5884
05:04:36,680 --> 05:04:39,040
TELL YOU ABOUT SOME UNPUBLISHED

5885
05:04:39,040 --> 05:04:40,480
WORK THAT HAS BEEN VERY

5886
05:04:40,480 --> 05:04:41,680
EXCITING.

5887
05:04:41,680 --> 05:04:44,680
USING THE SAME PIPELINE BUT

5888
05:04:44,680 --> 05:04:47,880
APPLYING IT TO GUT COMMUNITIES

5889
05:04:47,880 --> 05:04:51,920
FROM UNRELATED HUMAN DONORS.

5890
05:04:51,920 --> 05:04:54,240
BRIEFLY SOME OF THE DATA

5891
05:04:54,240 --> 05:04:56,480
EMERGING WHERE WHAT WE SEE IS

5892
05:04:56,480 --> 05:04:59,160
THAT THERE ARE INDIVIDUALS WITH

5893
05:04:59,160 --> 05:05:01,360
HIGHLY VARYING RATES OF

5894
05:05:01,360 --> 05:05:02,880
METABOLISM OF THESE DRUGS.

5895
05:05:02,880 --> 05:05:08,160
IN RED AND BLUE -- IN RED IS THE

5896
05:05:08,160 --> 05:05:10,360
SAME INDIVIDUAL AFTER INCUBATION

5897
05:05:10,360 --> 05:05:12,680
WITH TWO DIFFERENT DRUGS AND THE

5898
05:05:12,680 --> 05:05:14,160
INDIVIDUALS THAT HERE MOST

5899
05:05:14,160 --> 05:05:19,040
ACTIVE ON ONE ARE NOT THE ONES

5900
05:05:19,040 --> 05:05:20,880
THAT ARE THE MOST ACTIVE ON THE

5901
05:05:20,880 --> 05:05:21,320
OTHER.

5902
05:05:21,320 --> 05:05:23,320
THIS IS ALLOWING US TO MOVE

5903
05:05:23,320 --> 05:05:27,120
FORWARD FROM REDUCTIONIST

5904
05:05:27,120 --> 05:05:30,680
STUDIES OF SINGLE MICROBES TO

5905
05:05:30,680 --> 05:05:32,280
PREDICTING THE ACTIVITY.

5906
05:05:32,280 --> 05:05:35,600
SO WITH THAT I'LL END BY

5907
05:05:35,600 --> 05:05:37,040
HIGHLIGHTING THAT A MEDICAL DRUG

5908
05:05:37,040 --> 05:05:40,240
CAN SERVE AS TOOLS TO UNDERSTAND

5909
05:05:40,240 --> 05:05:44,240
HOW MICROBES CAN TRANSFORM IN

5910
05:05:44,240 --> 05:05:45,000
THEIR ENVIRONMENT.

5911
05:05:45,000 --> 05:05:47,920
AND THEN FINALLY I THINK THAT IN

5912
05:05:47,920 --> 05:05:50,800
THE NEXT ANIMATION -- WE SHOULD

5913
05:05:50,800 --> 05:05:54,280
START TO THINK ABOUT HOW THESE

5914
05:05:54,280 --> 05:05:55,360
MICROBIOME VARIATION THAT WE'RE

5915
05:05:55,360 --> 05:05:58,720
SEEING SHOULD DRIVE HOW MEDICAL

5916
05:05:58,720 --> 05:06:00,200
DRUGS ARE BEING DEVELOPED HOW

5917
05:06:00,200 --> 05:06:03,400
WE'RE MAKING SURE THEY ARE BEING

5918
05:06:03,400 --> 05:06:04,400
TESTED IN THE APPROPRIATE

5919
05:06:04,400 --> 05:06:06,040
PATIENT COHORT AND THINKING

5920
05:06:06,040 --> 05:06:10,120
ABOUT PREBIOTIC AND PRO-BIOTIC

5921
05:06:10,120 --> 05:06:11,400
THERAPIES THAT CAN BE INCLUDED

5922
05:06:11,400 --> 05:06:12,720
IN THE ADMINISTRATION OF THE

5923
05:06:12,720 --> 05:06:13,160
DRUGS.

5924
05:06:13,160 --> 05:06:14,680
WITH THAT I'LL STOP AND THANK

5925
05:06:14,680 --> 05:06:18,440
YOU.

5926
05:06:18,440 --> 05:06:19,080
>> DR. GOOD MAN.

5927
05:06:19,080 --> 05:06:20,320
THANK YOU FOR THAT EXCELLENT

5928
05:06:20,320 --> 05:06:20,840
TALK.

5929
05:06:20,840 --> 05:06:23,920
IF YOU REMEMBER WE WOULD TALK

5930
05:06:23,920 --> 05:06:25,360
ABOUT DRUG TOXICITY.

5931
05:06:25,360 --> 05:06:26,560
WE NEVER THOUGHT ABOUT THE

5932
05:06:26,560 --> 05:06:28,640
IMPACT OF THE MICROBIOME AND YOU

5933
05:06:28,640 --> 05:06:31,320
DID A WONDERFUL JOB OF

5934
05:06:31,320 --> 05:06:31,680
EXPLAINING THAT.

5935
05:06:31,680 --> 05:06:34,440
THANK YOU VERY MUCH.

5936
05:06:34,440 --> 05:06:36,440
>> THANK YOU DR. HAMILTON AND

5937
05:06:36,440 --> 05:06:38,080
ALL OF THE SPEAKERS.

5938
05:06:38,080 --> 05:06:40,200
DO YOU HAVE A COUPLE OF

5939
05:06:40,200 --> 05:06:41,760
CONTINUES BEFORE DR. VARRICCHIO

5940
05:06:41,760 --> 05:06:43,160
GAS TAKES OVER.

5941
05:06:43,160 --> 05:06:44,120
*

5942
05:06:44,120 --> 05:06:53,640
>> I'M TURN IT OVER TO DR.

5943
05:06:53,640 --> 05:07:06,400
DR. VARGAS.

5944
05:07:06,400 --> 05:07:11,600
>> THEY REALLY FOCUSED ON

5945
05:07:11,600 --> 05:07:13,560
PRECISION PRO-BIOTIC RESEARCH.

5946
05:07:13,560 --> 05:07:16,120
AND I JUST WANT TO SAY A BIG

5947
05:07:16,120 --> 05:07:19,240
THANK TO ALL OF THE SPEAKERS AND

5948
05:07:19,240 --> 05:07:19,640
ORGANIZERS.

5949
05:07:19,640 --> 05:07:23,440
AND AS WE MOVE INTO THIS LATE

5950
05:07:23,440 --> 05:07:25,280
AFTERNOON PANEL I HOPE TO KEEP

5951
05:07:25,280 --> 05:07:27,120
UP THE ENERGY AND START THE

5952
05:07:27,120 --> 05:07:28,000
DISCUSSION.

5953
05:07:28,000 --> 05:07:32,480
I'M GOING TO ASK SPEAKERS TO

5954
05:07:32,480 --> 05:07:34,640
RAISE THEIR HAND IF THEY HAVE

5955
05:07:34,640 --> 05:07:37,520
QUESTIONS AND FOR SPEAKERS FOR

5956
05:07:37,520 --> 05:07:39,320
THIS SESSION TURN YOUR VIDEO ON

5957
05:07:39,320 --> 05:07:41,440
AND UNMUTE YOURSELF WHEN YOU'RE

5958
05:07:41,440 --> 05:07:42,840
READY TO ANSWER A QUESTION.

5959
05:07:42,840 --> 05:07:44,080
IF YOU HAVE ADDITIONAL QUESTIONS

5960
05:07:44,080 --> 05:07:45,760
YOU WANT TO PUT IN THE CHAT THAT

5961
05:07:45,760 --> 05:07:47,840
IS FINE TOO.

5962
05:07:47,840 --> 05:07:50,480
WE'LL START WITH A QUESTION I

5963
05:07:50,480 --> 05:07:54,680
HAVE AND THEN I'LL LOOK FORAYED

5964
05:07:54,680 --> 05:07:57,240
HANDS.

5965
05:07:57,240 --> 05:07:59,000
SO I'M GOING TO START WITH

5966
05:07:59,000 --> 05:08:00,880
SOMETHING THAT REALLY STRUCK ME

5967
05:08:00,880 --> 05:08:03,560
AS I WAS LISTENING TO THE

5968
05:08:03,560 --> 05:08:05,280
PRESENTATIONS THIS AFTERNOON.

5969
05:08:05,280 --> 05:08:08,960
DR. DONOVAN AND OTHERS PRESENTED

5970
05:08:08,960 --> 05:08:10,440
NEW TECHNIQUES THAT ARE COMING

5971
05:08:10,440 --> 05:08:11,840
OUT AND THAT ARE AVAILABLE.

5972
05:08:11,840 --> 05:08:13,880
AND I THINK I WORK IN EARLY LIFE

5973
05:08:13,880 --> 05:08:16,440
SO I THINK ABOUT INFANTS AND HOW

5974
05:08:16,440 --> 05:08:18,840
WE NEED TO BE NONINVASIVE THERE.

5975
05:08:18,840 --> 05:08:20,960
BUT THERE ARE MANY OTHER REASONS

5976
05:08:20,960 --> 05:08:23,760
WHY WE NEED NONINVASIVE MEASURES

5977
05:08:23,760 --> 05:08:25,520
ESPECIALLY AS WE MOVE INTO AREAS

5978
05:08:25,520 --> 05:08:27,280
OF PREVENTION WHERE WE'RE

5979
05:08:27,280 --> 05:08:32,000
LOOKING AT HEALTHY INDIVIDUALS.

5980
05:08:32,000 --> 05:08:35,000
ARE THERE OTHER OPPORTUNITIES

5981
05:08:35,000 --> 05:08:37,840
WITHIN INFANTS, ADULTS, OLDER

5982
05:08:37,840 --> 05:08:40,280
ADULTS WHERE WE REALLY NEEDED

5983
05:08:40,280 --> 05:08:42,960
ADVANCES IN NONINVASIVE

5984
05:08:42,960 --> 05:08:45,920
TECHNOLOGY TO MOVE PRECISION

5985
05:08:45,920 --> 05:08:47,600
PRO-BIOTICS INTO CLINICAL

5986
05:08:47,600 --> 05:09:00,040
TRIALS?

5987
05:09:00,040 --> 05:09:03,360
>> ASHLEY, YOU HAVE A SHY GROUP.

5988
05:09:03,360 --> 05:09:06,040
>> IT IS 4:30.

5989
05:09:06,040 --> 05:09:10,040
>> I CAN MAKE A QUICK COMMENT.

5990
05:09:10,040 --> 05:09:15,240
I THINK THAT BASED ON THE

5991
05:09:15,240 --> 05:09:18,240
EXCELLENT WORK OF INDIVIDUALS

5992
05:09:18,240 --> 05:09:21,440
WHO PRESENTED THIS AFTERNOON AS

5993
05:09:21,440 --> 05:09:24,440
WELL AS OUR OWN BIAS OF SEEING

5994
05:09:24,440 --> 05:09:28,000
HOW INCREDIBLY VARIABLE THE

5995
05:09:28,000 --> 05:09:29,800
MICROBIOME IS NOT ONLY BETWEEN

5996
05:09:29,800 --> 05:09:31,680
INDIVIDUALS BUT WITHIN THE

5997
05:09:31,680 --> 05:09:32,840
INDIVIDUAL AS WELL.

5998
05:09:32,840 --> 05:09:38,360
I THINK THAT A LOT OF THE FACT

5999
05:09:38,360 --> 05:09:39,240
THAT THAT INDIVIDUALS HAVE TAKEN

6000
05:09:39,240 --> 05:09:41,600
IS ONE OF TRYING TO IDENTIFY

6001
05:09:41,600 --> 05:09:43,640
FUNCTIONS THAT THE BACTERIA DO

6002
05:09:43,640 --> 05:09:45,520
OR SMALL MOLECULES OR THINGS OF

6003
05:09:45,520 --> 05:09:48,160
THAT SORT AND ULTIMATELY IF WE

6004
05:09:48,160 --> 05:09:51,040
WANT TO FIND BETTER

6005
05:09:51,040 --> 05:09:56,520
TRANSLATIONAL METHODS THAT WORK

6006
05:09:56,520 --> 05:10:00,040
AT A MORE POPULATION LEVEL IN A

6007
05:10:00,040 --> 05:10:02,400
CLINICAL TRIAL AS DESCRIBED

6008
05:10:02,400 --> 05:10:04,240
EARLIER TODAY THAT WE REALLY

6009
05:10:04,240 --> 05:10:06,680
HAVE TO FIND SOMETHING THAT

6010
05:10:06,680 --> 05:10:08,800
BYPASSES THE MICROBIOME ITSELF

6011
05:10:08,800 --> 05:10:10,920
AND ACTUALLY PULLS ON THE LEAVES

6012
05:10:10,920 --> 05:10:13,960
THAT THE MICROBIOME PReSS.

6013
05:10:13,960 --> 05:10:19,120
I THINK THAT THAT IS PROBABLY

6014
05:10:19,120 --> 05:10:21,120
LIKE THE THEME THAT THESE SMALL

6015
05:10:21,120 --> 05:10:24,640
MOLECULES ARE -- WE'RE

6016
05:10:24,640 --> 05:10:26,200
DISCOVERING THAT THE MICROBIOME

6017
05:10:26,200 --> 05:10:30,560
IS USING THESE TO AFFECT THE

6018
05:10:30,560 --> 05:10:32,240
ECOLOGY AND WE HAVE TO USE THEM

6019
05:10:32,240 --> 05:10:34,760
IN A SIMILAR WAY TO DO SO IF WE

6020
05:10:34,760 --> 05:10:37,200
WANT TO DO WHAT THE MICROBIOME

6021
05:10:37,200 --> 05:10:39,200
IS DOING IN TERMS OF AFFECTING

6022
05:10:39,200 --> 05:10:40,040
HEALTH.

6023
05:10:40,040 --> 05:10:42,480
THAT IS A CONTINUING CONJECTURE

6024
05:10:42,480 --> 05:10:44,400
AND I THINK THIS ISSUE OF

6025
05:10:44,400 --> 05:10:47,480
VARIABILITY IS ONE THAT IT'S

6026
05:10:47,480 --> 05:10:56,280
PRETTY -- DIFFICULT TO DEAL WITH

6027
05:10:56,280 --> 05:10:56,480
WITH.

6028
05:10:56,480 --> 05:10:57,800
I'LL STOP THERE BECAUSE NOW

6029
05:10:57,800 --> 05:10:59,440
THERE ARE OTHER PEOPLE.

6030
05:10:59,440 --> 05:11:02,640
>> THANK YOU FOR THE COMMENT.

6031
05:11:02,640 --> 05:11:05,240
WONDERFUL COMMENT.

6032
05:11:05,240 --> 05:11:05,720
DR. ZHAO.

6033
05:11:05,720 --> 05:11:08,760
>> I HAVE A HIGH LEVEL COMMENT

6034
05:11:08,760 --> 05:11:11,200
ON THIS QUESTION.

6035
05:11:11,200 --> 05:11:15,440
YES, I AGREE THAT NOT ONLY THE

6036
05:11:15,440 --> 05:11:17,680
NONINVASIVE MEASURES ARE WHAT WE

6037
05:11:17,680 --> 05:11:19,240
NEED PARTICULARLY WITH CLINICAL

6038
05:11:19,240 --> 05:11:24,080
TRIALS AND ALSO WITH BABIES WITH

6039
05:11:24,080 --> 05:11:26,600
OLDER PEOPLE.

6040
05:11:26,600 --> 05:11:32,120
BUT IN GENERAL TAKING THE STOOL

6041
05:11:32,120 --> 05:11:35,760
SAMPLE AND IDENTIFYING THE

6042
05:11:35,760 --> 05:11:37,960
MICROBIOME IS A NONINVASIVE

6043
05:11:37,960 --> 05:11:40,720
TECHNOLOGY AND YOU ARE RIP AND

6044
05:11:40,720 --> 05:11:42,840
METABOLITES ANALYSIS IS ANOTHER

6045
05:11:42,840 --> 05:11:44,840
EXAMPLE OF A NONINVASIVE

6046
05:11:44,840 --> 05:11:45,440
TECHNOLOGY.

6047
05:11:45,440 --> 05:11:49,480
SO IF YOU LOOK AT URINE AND

6048
05:11:49,480 --> 05:11:54,040
STOOL IF YOU ALSO COUNT BLOOD

6049
05:11:54,040 --> 05:11:55,600
SAMPLE THAT IS THE LEAST

6050
05:11:55,600 --> 05:11:56,440
INVASIVE WAY.

6051
05:11:56,440 --> 05:11:58,880
SO THIS ACTUALLY CAN BE WIDELY

6052
05:11:58,880 --> 05:11:59,560
SEND.

6053
05:11:59,560 --> 05:12:03,520
SO URINE, BLOOD AND A FECAL

6054
05:12:03,520 --> 05:12:05,840
SAMPLE IS THREE WINDOWS.

6055
05:12:05,840 --> 05:12:09,320
AND ANY BIOLOGICAL MOLECULE IN

6056
05:12:09,320 --> 05:12:12,640
THESE THREE REASONS HAS A

6057
05:12:12,640 --> 05:12:13,640
MECHANISM.

6058
05:12:13,640 --> 05:12:18,160
IT'S A -- -- HAS VERY RICH

6059
05:12:18,160 --> 05:12:19,920
INFORMATION WHICH ACTUALLY

6060
05:12:19,920 --> 05:12:22,800
REFLECTS OUR HEALTH OR OUR

6061
05:12:22,800 --> 05:12:26,520
DISEASES AND COMPOUNDED BY DIET,

6062
05:12:26,520 --> 05:12:29,600
AGE, GENDER AND ALL KIND OF

6063
05:12:29,600 --> 05:12:31,360
THINGS.

6064
05:12:31,360 --> 05:12:33,640
WE DEFINITELY SHOULD MOVE TOWARD

6065
05:12:33,640 --> 05:12:35,840
THIS DIRECTION.

6066
05:12:35,840 --> 05:12:38,400
BUT WE NEED VERY DIFFERENT WAY

6067
05:12:38,400 --> 05:12:41,560
OF ANALYZING THE DATA AND AGAIN

6068
05:12:41,560 --> 05:12:44,440
I WOULD COMMENT THAT DO NOT RELY

6069
05:12:44,440 --> 05:12:48,040
ON THE DATABASE BUT LET THE DATA

6070
05:12:48,040 --> 05:12:48,880
SPEAK FOR ITSELF.

6071
05:12:48,880 --> 05:12:51,040
THAT IS VERY, VERY IMPORTANT.

6072
05:12:51,040 --> 05:12:52,880
>> AND WE'RE GOING TO COME BACK

6073
05:12:52,880 --> 05:12:55,120
TO THAT SPECIFICALLY.

6074
05:12:55,120 --> 05:12:57,960
I'M CURIOUS ABOUT YOUR THOUGHTS

6075
05:12:57,960 --> 05:12:59,360
ON THAT.

6076
05:12:59,360 --> 05:13:00,840
DR. ZIMMERMAN GO AHEAD.

6077
05:13:00,840 --> 05:13:03,520
>> THE COMMENT ABOUT NONINVASIVE

6078
05:13:03,520 --> 05:13:03,920
SAMPLING.

6079
05:13:03,920 --> 05:13:07,560
I THINK THE POINTS THAT WERE

6080
05:13:07,560 --> 05:13:09,840
BROUGHT UP ARE GOOD ONES.

6081
05:13:09,840 --> 05:13:13,400
WE HAVE A LOT OF GOOD METHODS

6082
05:13:13,400 --> 05:13:19,120
THAT REPORT ON A WIDE VARIETY OF

6083
05:13:19,120 --> 05:13:20,760
BIOLOGY GOING ON IN THE GUT.

6084
05:13:20,760 --> 05:13:23,960
WHAT WAS EXCITING IS THE

6085
05:13:23,960 --> 05:13:25,840
PROSPECT OF TAKING STOOL SAMPLES

6086
05:13:25,840 --> 05:13:27,600
AND GETTING A READE OUT OF WHAT

6087
05:13:27,600 --> 05:13:30,400
IS HAPPENING TO THE EPITHELIUM

6088
05:13:30,400 --> 05:13:31,880
IN THE SMALL INTESTINE.

6089
05:13:31,880 --> 05:13:33,800
IT'S ONE OF THE AREAS THAT HAS

6090
05:13:33,800 --> 05:13:35,800
BEEN SUPER HARD TO ACCESS AND

6091
05:13:35,800 --> 05:13:37,800
THERE HAVE BEEN A FEW CUTTING

6092
05:13:37,800 --> 05:13:40,080
EDGE STUDIES THAT HAVE DONE --

6093
05:13:40,080 --> 05:13:41,760
WORK IN THIS AREA.

6094
05:13:41,760 --> 05:13:43,440
THERE IS ADDITIONAL WORK GOING

6095
05:13:43,440 --> 05:13:45,520
ON LOOKING AT THE SMALL

6096
05:13:45,520 --> 05:13:46,760
INTESTINAL COMMUNITY.

6097
05:13:46,760 --> 05:13:49,960
THERE ARE CAPSULES NOW BEING PUT

6098
05:13:49,960 --> 05:13:53,400
THROUGH THAT OPEN UP AND COLLECT

6099
05:13:53,400 --> 05:13:58,840
SAMPLES AND MICROBE THAT'S

6100
05:13:58,840 --> 05:14:01,240
DEMONSTRATE THERE IS A DIFFERENT

6101
05:14:01,240 --> 05:14:02,640
COMMUNITY IN THE SMALL

6102
05:14:02,640 --> 05:14:03,120
INTESTINE.

6103
05:14:03,120 --> 05:14:05,240
JUST A TON OF INTERESTING

6104
05:14:05,240 --> 05:14:06,640
BIOLOGY GOING ON.

6105
05:14:06,640 --> 05:14:10,080
THAT'S AN AREA TO THINK B. HOW

6106
05:14:10,080 --> 05:14:17,760
CAN WE DECONVOLUTE SYMBOLS -- OR

6107
05:14:17,760 --> 05:14:21,280
DEVELOP TECHNOLOGIES THAT AND IT

6108
05:14:21,280 --> 05:14:25,560
MAY BE STOOL TRANSCRIPT --

6109
05:14:25,560 --> 05:14:28,440
NOMICS AND IT MAY BE CAPSULES

6110
05:14:28,440 --> 05:14:30,440
BUT A PUSH AND I THINK FOR A LOT

6111
05:14:30,440 --> 05:14:32,600
OF THE DISEASES THAT WE'RE

6112
05:14:32,600 --> 05:14:36,480
SEEING TAKE THE IMPACT OF THE

6113
05:14:36,480 --> 05:14:40,160
MICROBIOME ON RESPONSE TO IMMUNO

6114
05:14:40,160 --> 05:14:40,600
THERAPY.

6115
05:14:40,600 --> 05:14:42,240
WE STILL DON'T KNOW WHAT WE

6116
05:14:42,240 --> 05:14:45,760
SHOULD BE MEASURING.

6117
05:14:45,760 --> 05:14:48,200
AND SO TAKING MORE MEASUREMENTS

6118
05:14:48,200 --> 05:14:50,720
AND ADDITIONAL MEASUREMENTS IS

6119
05:14:50,720 --> 05:14:52,640
SUPER IMPORTANT AND I JUST

6120
05:14:52,640 --> 05:14:55,280
WANTED TO COMMENT ABOUT THE

6121
05:14:55,280 --> 05:14:57,440
BUTTONS THAT THE MICROBIOME IS

6122
05:14:57,440 --> 05:15:00,000
PUSHING ON AND I BROADLY AGREE

6123
05:15:00,000 --> 05:15:01,960
WITH THE COMMENT THAT IF YOU'RE

6124
05:15:01,960 --> 05:15:03,920
THINKING ABOUT TREATING A

6125
05:15:03,920 --> 05:15:04,920
DISEASE OR SPECIFIC INDICATION

6126
05:15:04,920 --> 05:15:07,240
AND YOU KNOW WHAT IMMUNE CELL

6127
05:15:07,240 --> 05:15:11,680
YOU NEED TO INDUCE OR WHAT BILE

6128
05:15:11,680 --> 05:15:17,440
ACID OR WHAT RECEPTOR -- I AGREE

6129
05:15:17,440 --> 05:15:17,920
WITH THIS.

6130
05:15:17,920 --> 05:15:20,200
BUT THE WAY THE FIELD SHOULD BE

6131
05:15:20,200 --> 05:15:23,480
THINKING IS CREATING MICROIAL

6132
05:15:23,480 --> 05:15:25,840
ECOLOGY THAT PREVENTS DISEASE

6133
05:15:25,840 --> 05:15:27,760
RATHER THAN TREATING DISEASE.

6134
05:15:27,760 --> 05:15:34,440
AND CREATING A HEALTHY ECOSYSTEM

6135
05:15:34,440 --> 05:15:44,040
-- SO I THINK ON THE ONE HAND WE

6136
05:15:44,040 --> 05:15:45,360
NEED TO THINK SPECIFICALLY ABOUT

6137
05:15:45,360 --> 05:15:47,560
WHAT WE'RE TARGETING AND ON THE

6138
05:15:47,560 --> 05:15:49,320
OTHER HAND WE SHOULD BE MOVING

6139
05:15:49,320 --> 05:15:51,160
TOWARDS THINKING ABOUT HOW TO

6140
05:15:51,160 --> 05:15:55,720
PREVENT CHRONIC INFLAMMATORY

6141
05:15:55,720 --> 05:15:56,000
DISEASES.

6142
05:15:56,000 --> 05:15:57,640
IF WE DON'T FIGURE OUT HOW TO

6143
05:15:57,640 --> 05:15:59,440
PREVENT THEM.

6144
05:15:59,440 --> 05:15:59,720
>> GREAT.

6145
05:15:59,720 --> 05:16:03,040
THANK YOU.

6146
05:16:03,040 --> 05:16:06,480
>> ONE ASPECT OF NONINVASIVE

6147
05:16:06,480 --> 05:16:08,160
IMAGING WHICH IS STILL APPEALING

6148
05:16:08,160 --> 05:16:09,840
BECAUSE IT'S PART OF MOST

6149
05:16:09,840 --> 05:16:11,920
PEOPLE'S CLINICAL CARE IS THE

6150
05:16:11,920 --> 05:16:15,440
USE OF IMAGING TO EITHER FIGURE

6151
05:16:15,440 --> 05:16:19,280
OUT THE METABOLIC ACTIVITY.

6152
05:16:19,280 --> 05:16:22,240
THE VERY WHAT REALLY HAVE IS THE

6153
05:16:22,240 --> 05:16:24,720
ABILITY TO MEASURE INTESTINAL

6154
05:16:24,720 --> 05:16:27,560
GAS WITHOUT ANY --

6155
05:16:27,560 --> 05:16:29,520
DIFFERENTIATION OF WHAT TYPE OF

6156
05:16:29,520 --> 05:16:30,840
GAS IT IS.

6157
05:16:30,840 --> 05:16:33,040
BUT IF YOU CAN BUILD ON

6158
05:16:33,040 --> 05:16:37,880
REALITIES -- THAT'S AN AREA OF

6159
05:16:37,880 --> 05:16:39,080
NEED BECAUSE IT'S SOMETHING THAT

6160
05:16:39,080 --> 05:16:41,440
WE CAN IMPLY MEANT DIRECTLY IN

6161
05:16:41,440 --> 05:16:43,400
THE CLINIC WITHOUT HAVING TO

6162
05:16:43,400 --> 05:16:46,560
COME UP WITH AN ENTIRELY NEW

6163
05:16:46,560 --> 05:16:48,800
PARADIGM BUT CAN BE HUGELY

6164
05:16:48,800 --> 05:16:50,240
INFORMATIVE IN THAT REGARD.

6165
05:16:50,240 --> 05:16:54,040
>> GREAT POINTS.

6166
05:16:54,040 --> 05:16:56,960
>> I'LL JUST ADD THAT I THINK

6167
05:16:56,960 --> 05:16:59,480
EVEN IF WE'RE LOOKING AT URINE

6168
05:16:59,480 --> 05:17:01,680
OR BLOOD THERE IS STILL I WOULD

6169
05:17:01,680 --> 05:17:03,640
REALLY PUSH FOR THE FACT THAT WE

6170
05:17:03,640 --> 05:17:07,040
STILL NEED A LOT OF BASIC

6171
05:17:07,040 --> 05:17:10,360
STANDARDIZATION AND I THINK

6172
05:17:10,360 --> 05:17:12,040
AMIR'S PRESENTATION ABOUT

6173
05:17:12,040 --> 05:17:13,320
CIRCADIAN RHYTHMS.

6174
05:17:13,320 --> 05:17:16,640
DO YOU COLLECT A 24 HOUR URINE

6175
05:17:16,640 --> 05:17:18,320
SAMPLE AND ALL OF THIS AND THE

6176
05:17:18,320 --> 05:17:19,840
TIMING.

6177
05:17:19,840 --> 05:17:22,640
SO I THINK THAT WE'RE AT A

6178
05:17:22,640 --> 05:17:25,240
JUMPING TOUR NOW WHERE * STUDIES

6179
05:17:25,240 --> 05:17:28,520
SHOULD BE FUNDED.

6180
05:17:28,520 --> 05:17:33,160
WE NEED IT TO BE FIGURING OUT

6181
05:17:33,160 --> 05:17:35,040
WHAT IS THE BEST WAY TO SAMPLE

6182
05:17:35,040 --> 05:17:37,480
AND PRESERVE SAMPLES AND THEY

6183
05:17:37,480 --> 05:17:39,680
WOULD BE A GOOD INVESTMENT OF

6184
05:17:39,680 --> 05:17:42,360
NIH TO HELP TO IDENTIFY WHAT

6185
05:17:42,360 --> 05:17:44,320
WOULD BE THESE MARKERS AND WHAT

6186
05:17:44,320 --> 05:17:46,680
IS THE BEST AND CONSISTENT WAY

6187
05:17:46,680 --> 05:17:48,600
AND COME UP WITH SOME GUIDANCE

6188
05:17:48,600 --> 05:17:51,160
SO THAT WE CAN COMPARE DATA AND

6189
05:17:51,160 --> 05:17:53,880
WE CAN DO MACHINE LEARNING AND

6190
05:17:53,880 --> 05:17:56,520
COMPARE ACROSS TIME.

6191
05:17:56,520 --> 05:17:59,520
I WAS STRUCK WITH YOUR DATA AND

6192
05:17:59,520 --> 05:18:01,280
I'M GLAD WE COLLECTED ALL OF THE

6193
05:18:01,280 --> 05:18:03,200
FIRST DIAPERS FROM OUR BABIES IN

6194
05:18:03,200 --> 05:18:05,040
THE MORNING.

6195
05:18:05,040 --> 05:18:14,240
BUT BABIES EAT 24 HOURS A DAY.

6196
05:18:14,240 --> 05:18:16,040
EVEN THOUGH WE'RE SAYING

6197
05:18:16,040 --> 05:18:18,800
SOMETHING LIKE BLOOD SAMPLES IS

6198
05:18:18,800 --> 05:18:21,000
NONINVASIVE IT'S STILL HIGHLY

6199
05:18:21,000 --> 05:18:24,720
INVASIVE FOR A HEALTHY INFANT.

6200
05:18:24,720 --> 05:18:27,000
SO I THINK THAT THERE IS STILL

6201
05:18:27,000 --> 05:18:29,520
OTHER METHODS THAT WE NEED TO

6202
05:18:29,520 --> 05:18:31,440
CONSIDER WITH INFANTS.

6203
05:18:31,440 --> 05:18:37,800
>> THANK YOU, DR. DONOVAN.

6204
05:18:37,800 --> 05:18:51,480
>> THANK YOU DR. VARRICCHIO GAS.

6205
05:18:51,480 --> 05:18:53,600
>> HEALTHY GUT MICRO BUY ON THE

6206
05:18:53,600 --> 05:18:57,120
A. IS IT THE SAME REGARDLESS OF

6207
05:18:57,120 --> 05:19:17,280
THE DIET OR THE ENVIRONMENT.

6208
05:19:17,280 --> 05:19:20,040
>> I HAVE TWO MORE QUESTIONS BUT

6209
05:19:20,040 --> 05:19:23,600
I'M STOP THERE AND GIVE PEOPLE A

6210
05:19:23,600 --> 05:19:25,640
CHANCE TO BECAUSE THE OTHERS ARE

6211
05:19:25,640 --> 05:19:35,040
DIFFERENT.

6212
05:19:35,040 --> 05:19:38,200
>> IT WOULD BE USEFUL TO KNOW IS

6213
05:19:38,200 --> 05:19:42,240
THAT THE BASELINE MICRO BIOTA?

6214
05:19:42,240 --> 05:19:43,040
PROBABLY NOT.

6215
05:19:43,040 --> 05:19:46,360
IF THEY WERE SICK AT BASELINE.

6216
05:19:46,360 --> 05:19:47,800
>> NOBODY IS ANSWERING IT.

6217
05:19:47,800 --> 05:19:50,760
I WOULD SAY WHAT WE SAID AT A

6218
05:19:50,760 --> 05:19:51,520
RECENT CONFERENCE.

6219
05:19:51,520 --> 05:19:52,440
IT'S TOUGH.

6220
05:19:52,440 --> 05:19:59,320
TO DEFINE A HEALTHY MICROBIOTA

6221
05:19:59,320 --> 05:20:01,400
IS SOMETHING THAT COMES UP.

6222
05:20:01,400 --> 05:20:03,920
THEY WANT TO MOVE TOWARDS THAT.

6223
05:20:03,920 --> 05:20:06,360
AND THE ONLY ANSWER IS HEALTHY

6224
05:20:06,360 --> 05:20:12,520
PEOPLE HAVE HEALTHY MICROBIOTA.

6225
05:20:12,520 --> 05:20:15,840
HOW DO WE DIVERSE SOMETHING IN

6226
05:20:15,840 --> 05:20:18,160
SOMEBODY THAT HAS NO OVERT

6227
05:20:18,160 --> 05:20:19,800
SYMPTOMS OF DISEASE.

6228
05:20:19,800 --> 05:20:23,720
BECAUSE PREVENTION FIELD IS

6229
05:20:23,720 --> 05:20:23,920
TOUGH.

6230
05:20:23,920 --> 05:20:26,080
TO KEEP YOU HEALTHY THERE IS NO

6231
05:20:26,080 --> 05:20:27,640
WAY TO MEASURE HEALTH AND WE

6232
05:20:27,640 --> 05:20:29,520
HAVE NOT FIGURED OUT HOW TO

6233
05:20:29,520 --> 05:20:31,320
MEASURE HEALTH SO HOW DO WE SAY

6234
05:20:31,320 --> 05:20:34,320
THAT WE NEED TO DO XY AND Z TO

6235
05:20:34,320 --> 05:20:36,680
PREVENT THEM FROM GETTING SICK

6236
05:20:36,680 --> 05:20:38,800
IT'S A DIFFERENT PERSPECTIVE

6237
05:20:38,800 --> 05:20:40,280
BECAUSE WE SEE PEOPLE WHO ARE

6238
05:20:40,280 --> 05:20:42,200
SICK BUT WE DO GET PEOPLE WHO

6239
05:20:42,200 --> 05:20:44,400
ARE HEALTHY WHO WANT TO DO

6240
05:20:44,400 --> 05:20:47,480
SOMETHING WITH THE MICROBIOME

6241
05:20:47,480 --> 05:20:49,520
AND OFTEN TIMES IT'S MORE

6242
05:20:49,520 --> 05:20:50,360
HARMFUL.

6243
05:20:50,360 --> 05:20:51,840
>> GREAT POINTS.

6244
05:20:51,840 --> 05:20:54,360
>> YES.

6245
05:20:54,360 --> 05:20:56,800
SO AGAIN WHAT IS A HEALTHY

6246
05:20:56,800 --> 05:20:57,640
MICROBIOME?

6247
05:20:57,640 --> 05:20:59,920
THIS IS THE HOLY GRAIL AND THE

6248
05:20:59,920 --> 05:21:01,040
FUNDAMENTAL QUESTION FOR THE

6249
05:21:01,040 --> 05:21:03,640
WHOLE FIELD.

6250
05:21:03,640 --> 05:21:05,960
IT IS CHALLENGING TO ANSWER THAT

6251
05:21:05,960 --> 05:21:06,960
QUESTION.

6252
05:21:06,960 --> 05:21:09,960
HOWEVER IT IS DOABLE TO ANSWER A

6253
05:21:09,960 --> 05:21:13,240
DIFFERENT QUESTION.

6254
05:21:13,240 --> 05:21:15,600
IF YOU HAVE TWO MICROBIOME

6255
05:21:15,600 --> 05:21:19,440
SAMPLES FROM THE SAME PERSON --

6256
05:21:19,440 --> 05:21:21,000
AND COLLECTED WITH ALL OF THE

6257
05:21:21,000 --> 05:21:22,720
MEDICAL DATA.

6258
05:21:22,720 --> 05:21:26,120
WHICH ONE IS THE HEALTHIER.

6259
05:21:26,120 --> 05:21:30,040
THIS QUESTION IS POSSIBLE -- --

6260
05:21:30,040 --> 05:21:33,680
THIS IS WHY WE USE HIGH FIBER

6261
05:21:33,680 --> 05:21:35,240
DIETS TO DO THE INTERVENTION.

6262
05:21:35,240 --> 05:21:39,320
AND THEN WE SEE -- CHANGES OF

6263
05:21:39,320 --> 05:21:42,120
THE MEDICAL PARAMETERS AND THEN

6264
05:21:42,120 --> 05:21:43,440
WE ARE ABLE TO ANSWER THE

6265
05:21:43,440 --> 05:21:44,640
QUESTION.

6266
05:21:44,640 --> 05:21:46,800
OF AFTER HIGH FIBER INTERVENTION

6267
05:21:46,800 --> 05:21:51,600
THE HOST BECOMES HEALTHIER AND

6268
05:21:51,600 --> 05:21:54,000
THE ASSOCIATED NEW MICROBIOME

6269
05:21:54,000 --> 05:21:55,760
PROBABLY CAN BE CONSIDERED A

6270
05:21:55,760 --> 05:21:58,280
HEALTHIER MICROBIOME.

6271
05:21:58,280 --> 05:22:00,520
SO WORKING ON THIS QUESTION ALL

6272
05:22:00,520 --> 05:22:03,040
TOGETHER WITH DIFFERENT

6273
05:22:03,040 --> 05:22:04,520
APPROACHES DIFFERENT

6274
05:22:04,520 --> 05:22:06,200
INTERVENTIONS AND EVENTUALLY THE

6275
05:22:06,200 --> 05:22:07,760
WHOLE FIELD MAY BE ABLE TO

6276
05:22:07,760 --> 05:22:10,440
ANSWER THE QUESTION.

6277
05:22:10,440 --> 05:22:11,080
>> OPTIMISTIC.

6278
05:22:11,080 --> 05:22:19,480
I LIKE IT.

6279
05:22:19,480 --> 05:22:22,920
>> -- -- THERE ARE PARTS OF THE

6280
05:22:22,920 --> 05:22:24,840
WORLD WHICH EAT A HIGH FIBER

6281
05:22:24,840 --> 05:22:27,440
DIET AND WE KNOW THAT THE

6282
05:22:27,440 --> 05:22:29,080
WESTERN WORLD DOES NOT BUT IF

6283
05:22:29,080 --> 05:22:32,160
YOU LOOK AT THE LIFE EXPECTANCY

6284
05:22:32,160 --> 05:22:34,280
THERE ARE REASONS FOR THAT.

6285
05:22:34,280 --> 05:22:37,160
THE LIFE SPECK TACT SEE OF

6286
05:22:37,160 --> 05:22:38,720
PEOPLE IN THE WESTERN WORLD WHO

6287
05:22:38,720 --> 05:22:40,560
DO NOT CONSUME THAT STILL SEEMS

6288
05:22:40,560 --> 05:22:45,000
TO BE LONGER.

6289
05:22:45,000 --> 05:22:47,840
* HOW DO YOU DEFINE HEALTH IN

6290
05:22:47,840 --> 05:22:59,840
THIS INSTANCE?

6291
05:22:59,840 --> 05:23:02,080
>> THIS IS ACTUALLY A VERY

6292
05:23:02,080 --> 05:23:03,040
INTERESTING QUESTION.

6293
05:23:03,040 --> 05:23:07,080
I WOULD LIKE TO COMMENT AGAIN.

6294
05:23:07,080 --> 05:23:09,960
WHEN WE SAY HIGH FIBER DIET IT'S

6295
05:23:09,960 --> 05:23:11,200
NOT ANY FIBER.

6296
05:23:11,200 --> 05:23:16,160
AND SO IF YOU LOOK AT PEOPLE AT

6297
05:23:16,160 --> 05:23:18,080
A HIGH LEVEL, TALKING ABOUT THE

6298
05:23:18,080 --> 05:23:22,360
HIGH FIBER DIETS IN THOSE UNDER

6299
05:23:22,360 --> 05:23:24,920
DEVELOPED AREAS MOST MAY CONSUME

6300
05:23:24,920 --> 05:23:27,960
THE HIGH NONFERMENTABLE FIBER

6301
05:23:27,960 --> 05:23:30,280
AND ALSO THEY HAVE VERY LOW

6302
05:23:30,280 --> 05:23:33,160
PROTEIN INTAKE AND MANY OTHER

6303
05:23:33,160 --> 05:23:36,760
ISSUES.

6304
05:23:36,760 --> 05:23:39,160
SO ITS NOT ANY FIBER.

6305
05:23:39,160 --> 05:23:41,160
IT HAS TO BE THE COMBINES OF

6306
05:23:41,160 --> 05:23:44,920
FIBER WHICH CAN PROMOTE THE

6307
05:23:44,920 --> 05:23:48,320
BENEFICIAL PART OF YOUR

6308
05:23:48,320 --> 05:23:51,560
MICROBIOME AND THEN -- ---SO WE

6309
05:23:51,560 --> 05:23:54,400
FOR EXAMPLE IF YOU LOOK AT THE

6310
05:23:54,400 --> 05:23:57,640
-- THE DATA -- TOTAL INCREASE OF

6311
05:23:57,640 --> 05:24:01,040
TOTAL FIBER INTAKE ASSOCIATED

6312
05:24:01,040 --> 05:24:05,080
WITH THIS PREVENTION -- OF

6313
05:24:05,080 --> 05:24:06,960
COLLIN CANCER FOR EXAMPLE.

6314
05:24:06,960 --> 05:24:11,040
-- -- INTO VEGETABLE AND FOOT

6315
05:24:11,040 --> 05:24:14,800
FIBER AND GREEN BASED FIBER --

6316
05:24:14,800 --> 05:24:17,640
ACTUALLY HAS -- BECAUSE

6317
05:24:17,640 --> 05:24:21,720
VEGETABLE AND FRUIT FIBER ARE

6318
05:24:21,720 --> 05:24:23,360
MOSTLY NONPERFECTMENTABLE.

6319
05:24:23,360 --> 05:24:28,720
THEY HAVE PHYSICAL EFFECT -- --

6320
05:24:28,720 --> 05:24:31,600
BUT MOST OF THE FIBER IN THOSE

6321
05:24:31,600 --> 05:24:34,600
PLANTS THEY ARE NONFERMENTABLE

6322
05:24:34,600 --> 05:24:37,680
AND THEY DO NOT PRODUCE CERTAIN

6323
05:24:37,680 --> 05:24:38,440
ACIDS.

6324
05:24:38,440 --> 05:24:43,720
SO WE NEEDED TO BE MORE INTO THE

6325
05:24:43,720 --> 05:24:46,600
QUESTION -- AND NOT TO HAVE A

6326
05:24:46,600 --> 05:24:49,680
GENERAL HIGH FIBER AS AN

6327
05:24:49,680 --> 05:24:51,480
UMBRELLA.

6328
05:24:51,480 --> 05:24:52,480
>> SPECIFICS ARE IMPORTANT.

6329
05:24:52,480 --> 05:24:53,800
GOOD POINT.

6330
05:24:53,800 --> 05:24:57,720
I'M GOING TO MOVE TO DR. -- SON

6331
05:24:57,720 --> 05:24:59,680
ENSBERG.

6332
05:24:59,680 --> 05:25:01,200
>> I JUST WANTED TO COMMENT ON

6333
05:25:01,200 --> 05:25:05,240
THE HEALTHY MICROBIOME QUESTION

6334
05:25:05,240 --> 05:25:06,680
BECAUSE ALL OF THE COMMENTS ARE

6335
05:25:06,680 --> 05:25:12,600
RIGHT -- ON POINT.

6336
05:25:12,600 --> 05:25:15,360
THERE ARE THEY KINDS OF COMMON

6337
05:25:15,360 --> 05:25:17,120
FEATURES THAT APPEAR TO BE

6338
05:25:17,120 --> 05:25:18,760
ASSOCIATED WITH HEALTH.

6339
05:25:18,760 --> 05:25:22,200
LIKE -- PRODUCTION APPEARS TO BE

6340
05:25:22,200 --> 05:25:23,680
SOMETHING THAT MOST STUDIES ARE

6341
05:25:23,680 --> 05:25:25,240
FINDING MORE OF THAT IN THE

6342
05:25:25,240 --> 05:25:27,840
CONTEXT OF A WESTERN MICRO

6343
05:25:27,840 --> 05:25:29,240
BIOTAS HEALTHIER.

6344
05:25:29,240 --> 05:25:31,640
SAME WITH DIVERSITY.

6345
05:25:31,640 --> 05:25:33,200
NOT NECESSARILY THAT YOU WANT

6346
05:25:33,200 --> 05:25:35,520
MORE DIVERSITY BUT IN THE

6347
05:25:35,520 --> 05:25:38,840
CONTEXT OF THE MICROBIOTA MORE

6348
05:25:38,840 --> 05:25:41,240
DIVERSITY SEEMS TO BE BETTER.

6349
05:25:41,240 --> 05:25:44,280
OUTGROWTHS OF BACTERIA SEEMS TO

6350
05:25:44,280 --> 05:25:46,560
BE BAD AND ASSOCIATED WITH

6351
05:25:46,560 --> 05:25:47,240
INFLAMMATION.

6352
05:25:47,240 --> 05:25:51,640
BUT A BIGGER ISSUE -- ABOUT

6353
05:25:51,640 --> 05:25:56,000
FIRST OF ALL THE QUESTION OF

6354
05:25:56,000 --> 05:25:56,440
LIFE-SPAN.

6355
05:25:56,440 --> 05:25:58,040
THAT IS A GOOD ONE AND ONE THAT

6356
05:25:58,040 --> 05:26:02,040
WE HAVE TO GRAPPLE WITH.

6357
05:26:02,040 --> 05:26:03,840
COMPARING THE LIFE-SPAN WITH

6358
05:26:03,840 --> 05:26:06,240
THOSE THAT LIVE IN LOW AND

6359
05:26:06,240 --> 05:26:08,920
MIDDLE INCOME COUNTRIES IS NOT A

6360
05:26:08,920 --> 05:26:09,880
FAIR COMPARISON.

6361
05:26:09,880 --> 05:26:13,840
BECAUSE IF WE HAD A BETTER MICRO

6362
05:26:13,840 --> 05:26:15,760
BUY OAT AM WE MIGHT BE ABLE TO

6363
05:26:15,760 --> 05:26:16,680
LIVE LONGER.

6364
05:26:16,680 --> 05:26:19,560
*.

6365
05:26:19,560 --> 05:26:21,760
THE OTHER ISSUE IS HOW -- IF YOU

6366
05:26:21,760 --> 05:26:25,800
LOOK AT THE MICROBIOTA OF A

6367
05:26:25,800 --> 05:26:29,280
HEALTHY PERSON -- WHAT PLAGUES

6368
05:26:29,280 --> 05:26:31,400
US ARE THE CHRONIC DISEASES AND

6369
05:26:31,400 --> 05:26:33,480
THOSE USUALLY TAKE DECADES TO

6370
05:26:33,480 --> 05:26:33,960
DEVELOP.

6371
05:26:33,960 --> 05:26:35,920
THE QUESTION IS IF YOU LOOK AT A

6372
05:26:35,920 --> 05:26:37,160
HEALTHY PERSON DO THEY

6373
05:26:37,160 --> 05:26:40,040
NECESSARILY HAVE A HEALTHY

6374
05:26:40,040 --> 05:26:42,880
MICROBIOTA -- OR ONE THAT IS

6375
05:26:42,880 --> 05:26:45,080
PROMOTING THE VERY INFLAMMATION

6376
05:26:45,080 --> 05:26:47,440
A DECADE OR TWO DOWN THE ROAD IS

6377
05:26:47,440 --> 05:26:49,560
GOING TO CAUSE THEM TO HAVE SOME

6378
05:26:49,560 --> 05:26:50,760
TERRIBLE DISEASE.

6379
05:26:50,760 --> 05:26:54,440
SO IT'S HARD TO SAY THAT HEALTHY

6380
05:26:54,440 --> 05:26:56,680
PEOPLE HAVE HEALTHY MICRO

6381
05:26:56,680 --> 05:26:59,880
BIOTAS.

6382
05:26:59,880 --> 05:27:02,080
* SO IT'S A BIG CHALLENGE AND

6383
05:27:02,080 --> 05:27:03,640
THE WAY THAT WE'VE BEEN THINKING

6384
05:27:03,640 --> 05:27:07,960
ABOUT THIS ONE WAY IS TO TURN AN

6385
05:27:07,960 --> 05:27:16,480
EVOLUTIONARY FILTER ON THIS.

6386
05:27:16,480 --> 05:27:18,600
JUST THAT IT MAY REPRESENT A

6387
05:27:18,600 --> 05:27:22,120
STATE THAT OUR HUMAN GENOME

6388
05:27:22,120 --> 05:27:24,240
EVOLVED WITH AND THERE MAY BE

6389
05:27:24,240 --> 05:27:27,280
FEATURES THAT ARE HUMAN GENOME

6390
05:27:27,280 --> 05:27:30,160
HAS COME TO INSPECTOR MAYBE MORE

6391
05:27:30,160 --> 05:27:31,080
ACCUSTOMED TO.

6392
05:27:31,080 --> 05:27:40,760
A SIMPLE EXAMPLE IS - --

6393
05:27:40,760 --> 05:27:48,880
DEGRADATION.

6394
05:27:48,880 --> 05:27:50,800
AND WE ALSO KNOW THAT IF YOU

6395
05:27:50,800 --> 05:27:52,560
DON'T HAVE THAT SPECIES YOU'RE

6396
05:27:52,560 --> 05:27:55,240
MORE LIKELY TO DEVELOP KIDNEY

6397
05:27:55,240 --> 05:27:57,000
STONES.

6398
05:27:57,000 --> 05:27:58,280
AND SO, THAT IS JUST AN EXAMPLE

6399
05:27:58,280 --> 05:28:02,000
OF A FUNCTION THAT WE'RE LOSING

6400
05:28:02,000 --> 05:28:05,160
DURING IN DUST SITUATION THAT IS

6401
05:28:05,160 --> 05:28:07,960
LEADING TO ANOTHER * DISEASE

6402
05:28:07,960 --> 05:28:11,360
THAT IS A PROTOTYPIC WESTERN

6403
05:28:11,360 --> 05:28:12,640
DISEASE, KIDNEY STONES.

6404
05:28:12,640 --> 05:28:14,120
SO, THAT IS ONE EXAMPLE OF

6405
05:28:14,120 --> 05:28:15,920
BRINGING BACK A FUNCTION -- EVEN

6406
05:28:15,920 --> 05:28:18,760
THOUGH MOST OF US HAVE MAYBE

6407
05:28:18,760 --> 05:28:21,080
HEALTHY MICROBIOMES WE MAY BE

6408
05:28:21,080 --> 05:28:23,640
MISSING THAT AND AT INCREASED

6409
05:28:23,640 --> 05:28:27,760
RISK FOR THAT DISEASE.

6410
05:28:27,760 --> 05:28:30,440
SO ANY WAY JUST SOME THOUGHTS.

6411
05:28:30,440 --> 05:28:34,720
>> THANK YOU.

6412
05:28:34,720 --> 05:28:36,680
>> I AGREE.

6413
05:28:36,680 --> 05:28:39,720
THE PROBLEM IS THE FEAR OF THE

6414
05:28:39,720 --> 05:28:41,040
UNKNOWN.

6415
05:28:41,040 --> 05:28:46,040
IN TERMS OF MOST THINGS CAN BE

6416
05:28:46,040 --> 05:28:49,440
TOLD AS SAYING YOU CAN EAT THIS

6417
05:28:49,440 --> 05:28:51,240
TO STAY HEALTHY.

6418
05:28:51,240 --> 05:28:54,040
WE DON'T KNOW ABOUT THE CHANGE.

6419
05:28:54,040 --> 05:28:56,840
IF WE KNEW WHAT THAT CHANGE WAS

6420
05:28:56,840 --> 05:28:58,640
THAT 20 YEARS LATER IS GOING TO

6421
05:28:58,640 --> 05:29:02,040
TRIGGER A DISEASE WE CAN SAY

6422
05:29:02,040 --> 05:29:02,600
OKAY.

6423
05:29:02,600 --> 05:29:04,160
THAT IS SOMETHING TO BE

6424
05:29:04,160 --> 05:29:04,680
TARGETED.

6425
05:29:04,680 --> 05:29:06,920
BUT RIGHT NOW IT'S THE FAST

6426
05:29:06,920 --> 05:29:09,480
UNKNOWN.

6427
05:29:09,480 --> 05:29:11,840
PEOPLE WHO COME TO SEE YOU WANT

6428
05:29:11,840 --> 05:29:12,400
TO KNOW.

6429
05:29:12,400 --> 05:29:14,200
AND WE DON'T KNOW IT AND THEY

6430
05:29:14,200 --> 05:29:16,240
WANT YOU TO FIX IT WITHOUT US

6431
05:29:16,240 --> 05:29:16,640
KNOWING IT.

6432
05:29:16,640 --> 05:29:19,520
SO, ITS A MATTER OF PRACTICAL

6433
05:29:19,520 --> 05:29:21,840
VERSUS CONCEPTUAL.

6434
05:29:21,840 --> 05:29:28,240
SO I COMPLETELY AGREE THAT --

6435
05:29:28,240 --> 05:29:31,040
BUT IF WE DON'T KNOW IT IS THIS

6436
05:29:31,040 --> 05:29:33,360
THE RIGHT TIME TO GO AFTER IT.

6437
05:29:33,360 --> 05:29:35,240
I'M NOT SAYING WE SHOULD STOP

6438
05:29:35,240 --> 05:29:36,120
LOOKING FOR IT.

6439
05:29:36,120 --> 05:29:38,440
BUT IN REALTIME -- THAT IS WHERE

6440
05:29:38,440 --> 05:29:44,640
THE CHALLENGE IS.

6441
05:29:44,640 --> 05:29:47,320
>> I COMPLETELY APPRECIATE THAT.

6442
05:29:47,320 --> 05:29:50,640
>> WE'LL HAVE THE LAST COMMENT

6443
05:29:50,640 --> 05:29:54,640
FROM DR. -- ZHAO AND THEN MOVE

6444
05:29:54,640 --> 05:29:55,040
ON.

6445
05:29:55,040 --> 05:29:57,920
>> IT IS POSSIBLE TO APPLY

6446
05:29:57,920 --> 05:29:59,160
INTERVENTIONS THAT CAN CHANGE

6447
05:29:59,160 --> 05:30:00,920
THE MICROBIOME.

6448
05:30:00,920 --> 05:30:02,280
WHICH WILL BE IN THE TIME FRAME

6449
05:30:02,280 --> 05:30:04,720
OF A FEW MONTHS INSTEAD OF YOU

6450
05:30:04,720 --> 05:30:07,240
NEED TO WAIT MANY YEARS AND YOU

6451
05:30:07,240 --> 05:30:09,480
NEED TO HAVE PREVIOUS SAMPLES

6452
05:30:09,480 --> 05:30:11,680
AND WAIT UNTIL THE DISEASE

6453
05:30:11,680 --> 05:30:13,920
MANIFEST AND THEN YOU COMPARE

6454
05:30:13,920 --> 05:30:17,320
AFTER AND TRY TO IDENTIFY

6455
05:30:17,320 --> 05:30:21,840
SOMETHING WHICH CAN PREDICT THE

6456
05:30:21,840 --> 05:30:23,760
RISK.

6457
05:30:23,760 --> 05:30:27,320
I PREFER INTERVENTION TRIALS

6458
05:30:27,320 --> 05:30:30,560
WHICH CAN CHANGE THE MICROBIOME

6459
05:30:30,560 --> 05:30:32,800
NOW RATHER THAN WAIT MANY

6460
05:30:32,800 --> 05:30:35,120
DECADES TO SEE HOW THE AGE

6461
05:30:35,120 --> 05:30:39,560
RELATED CHANGE OF THE MICROBIOME

6462
05:30:39,560 --> 05:30:42,880
ACTUALLY DRIVES THE RISK.

6463
05:30:42,880 --> 05:30:44,560
>> CAN I JUST MAKE A QUICK

6464
05:30:44,560 --> 05:30:45,080
POINT.

6465
05:30:45,080 --> 05:30:47,840
I KNOW A COUPLE OF YEARS AGO

6466
05:30:47,840 --> 05:30:50,520
STEVEN O'KEEFE AND -- PUBLISHED

6467
05:30:50,520 --> 05:30:52,960
A NICE PAPER WHERE THEY WERE IN

6468
05:30:52,960 --> 05:30:55,520
AFRICA AND AFRICANS AND THEM

6469
05:30:55,520 --> 05:30:56,520
AFRICAN-AMERICANS IN

6470
05:30:56,520 --> 05:30:59,040
PHILADELPHIA AND THEY BASICALLY

6471
05:30:59,040 --> 05:31:00,680
SWAPPED THE DIETS.

6472
05:31:00,680 --> 05:31:05,080
THEY WENT TO AFTER AFFECTED THEM

6473
05:31:05,080 --> 05:31:08,160
HAMBURGERS AND AFRICAN-AMERICANS

6474
05:31:08,160 --> 05:31:10,920
SORT OF A TRADITIONAL DIET.

6475
05:31:10,920 --> 05:31:13,880
AND WITHIN DAYS THEY COULD SEE

6476
05:31:13,880 --> 05:31:16,640
THROUGH BIOPSIES -- CHANGES IN

6477
05:31:16,640 --> 05:31:19,240
GENE EXPRESSION AND CHANGES IN

6478
05:31:19,240 --> 05:31:19,640
PROLIFERATION.

6479
05:31:19,640 --> 05:31:21,720
SO IT'S NOT EVEN MONTHS.

6480
05:31:21,720 --> 05:31:23,880
AND THAT WAS A WHOLE SIGNATURE.

6481
05:31:23,880 --> 05:31:25,480
IT WAS INVASIVE BECAUSE THEY

6482
05:31:25,480 --> 05:31:27,120
TODAY DO A BIOPSY.

6483
05:31:27,120 --> 05:31:29,040
BUT I THINK THAT WE DON'T HAVE

6484
05:31:29,040 --> 05:31:31,560
TO WAIT DECADES NECESSARILY.

6485
05:31:31,560 --> 05:31:32,920
THERE COULD BE SOME QUICKER

6486
05:31:32,920 --> 05:31:36,440
TYPES OF ASSAYS THAT COULD BE

6487
05:31:36,440 --> 05:31:38,000
DONE AND YOU CAN SCREEN

6488
05:31:38,000 --> 05:31:39,960
DIFFERENT PRO-BIOTICS IF YOU

6489
05:31:39,960 --> 05:31:42,640
HAVE THE BIOMARKERS OF WHATEVER

6490
05:31:42,640 --> 05:31:49,160
OUTCOMES YOU'RE LOOKING FOR.

6491
05:31:49,160 --> 05:31:49,720
>> EXCELLENT.

6492
05:31:49,720 --> 05:31:52,600
AND ON A POSITIVE NOTE.

6493
05:31:52,600 --> 05:31:54,080
BARBARA, DO YOU HAVE ADDITIONAL

6494
05:31:54,080 --> 05:31:55,840
QUESTIONS THAT YOU WANTED TO ASK

6495
05:31:55,840 --> 05:31:57,840
AT THIS TIME?

6496
05:31:57,840 --> 05:31:58,640
>> SURE.

6497
05:31:58,640 --> 05:32:01,600
I'M HAPPY TO ASK MORE QUESTIONS.

6498
05:32:01,600 --> 05:32:06,040
AS WE THINK ABOUT LOOKING AT

6499
05:32:06,040 --> 05:32:09,480
THIS SMALL MOLECULE METABOLITES

6500
05:32:09,480 --> 05:32:13,320
GENERATED BY OUR MICRO GUT IN

6501
05:32:13,320 --> 05:32:13,760
PICK.

6502
05:32:13,760 --> 05:32:17,760
WHAT KIND OF SAMPLE SIZE YOU

6503
05:32:17,760 --> 05:32:20,600
WOULD NEED IF YOU ARE LOOKING AT

6504
05:32:20,600 --> 05:32:24,160
METABOLITES OR URINE OR FECES TO

6505
05:32:24,160 --> 05:32:29,400
UNDERSTAND -- TO BE ABLE TO MAKE

6506
05:32:29,400 --> 05:32:30,840
PREDICTIONS ABOUT WHO'S GOING TO

6507
05:32:30,840 --> 05:32:33,640
HAVE WHAT RESPONSE TO A GIVEN

6508
05:32:33,640 --> 05:32:34,640
INTERVENTION BECAUSE YOU'RE

6509
05:32:34,640 --> 05:32:36,760
LOOKING ACROSS ALL KINDS OF

6510
05:32:36,760 --> 05:32:38,960
BACKGROUND DIETS AND GENOTYPES.

6511
05:32:38,960 --> 05:32:41,720
ALL KINDS OF DRUG EXPOSER AND

6512
05:32:41,720 --> 05:32:44,400
OTHER ENVIRONMENTAL EXPOSURES.

6513
05:32:44,400 --> 05:32:47,440
AS WELL AS DIFFERENT BASELINE

6514
05:32:47,440 --> 05:32:47,880
MICROBIOTA.

6515
05:32:47,880 --> 05:32:50,760
SO I'M WONDERING WHAT KIND OF

6516
05:32:50,760 --> 05:32:54,640
SAMPLE SIZE WOULD YOU NEED TO BE

6517
05:32:54,640 --> 05:32:56,640
ABLE TO SEE AN EFFECT AGAINST

6518
05:32:56,640 --> 05:32:58,200
THAT BACKGROUND VARIABILITY.

6519
05:32:58,200 --> 05:32:59,640
THAT IS ONE OF THE CENTRAL

6520
05:32:59,640 --> 05:33:03,320
QUESTIONS FOR THIS WORKSHOP?

6521
05:33:03,320 --> 05:33:05,640
HOW DOES THAT HELP YOU BE ABLE

6522
05:33:05,640 --> 05:33:10,760
TO PREDICT --

6523
05:33:10,760 --> 05:33:12,880
>> YOU BROKE UP A LITTLE BIT

6524
05:33:12,880 --> 05:33:15,640
>> ARE YOU ASKING HUNDREDS,

6525
05:33:15,640 --> 05:33:17,200
THOUSANDS, TENS OF THOUSANDS.

6526
05:33:17,200 --> 05:33:19,200
A BALLPARK?

6527
05:33:19,200 --> 05:33:20,640
>> IT'S A GREAT QUESTION AND I'M

6528
05:33:20,640 --> 05:33:26,640
NOT GOING TO GIVE A VERY

6529
05:33:26,640 --> 05:33:27,240
SATISFYING ANSWER.

6530
05:33:27,240 --> 05:33:29,320
BUT WHAT WE'VE LEARNED WHERE

6531
05:33:29,320 --> 05:33:31,200
WE'VE LOOKED AT TENS TO

6532
05:33:31,200 --> 05:33:33,760
HUNDREDS' THOUSANDS OF

6533
05:33:33,760 --> 05:33:35,080
INTERACTIONS BETWEEN SMALL

6534
05:33:35,080 --> 05:33:36,880
MOLECULES AND MICROBES IS THAT

6535
05:33:36,880 --> 05:33:39,800
WE SEE THE ENTIRE SPECTRUM OF

6536
05:33:39,800 --> 05:33:40,640
SIGNAL.

6537
05:33:40,640 --> 05:33:42,800
SOME OF WHICH WE WOULD SEE WITH

6538
05:33:42,800 --> 05:33:43,920
FIVE INDIVIDUALS AND OTHERS

6539
05:33:43,920 --> 05:33:45,480
WHERE WE'RE ONLY SEEING IT

6540
05:33:45,480 --> 05:33:46,520
BECAUSE OF THE DEPTH THAT WE

6541
05:33:46,520 --> 05:33:47,040
HAVE.

6542
05:33:47,040 --> 05:33:48,960
SO I THINK IT'S GOING TO BE VERY

6543
05:33:48,960 --> 05:33:53,840
HARD TO SAY THAT THE NUMBER IS

6544
05:33:53,840 --> 05:33:55,680
235 PEOPLE OR SOMETHING LIKE

6545
05:33:55,680 --> 05:33:57,000
THAT BUT MAYBE WE SHOULD THINK

6546
05:33:57,000 --> 05:34:00,480
ABOUT WAVES OF STUDY THAT ALLOW

6547
05:34:00,480 --> 05:34:03,600
US TO TRY TO DO A POWER ANALYSIS

6548
05:34:03,600 --> 05:34:06,000
BECAUSE I THINK THERE IS NOT

6549
05:34:06,000 --> 05:34:07,600
GOING TO BE ONE ANSWER.

6550
05:34:07,600 --> 05:34:09,840
8 BUT IF THERE ARE PILOT STUDIES

6551
05:34:09,840 --> 05:34:12,320
THAT GIVE US A SENSE OF THE

6552
05:34:12,320 --> 05:34:15,640
DEPTH IT MAY HAVE TO BE

6553
05:34:15,640 --> 05:34:16,840
INDIVIDUALLY DETERMINED FOR EACH

6554
05:34:16,840 --> 05:34:19,680
STUDY.

6555
05:34:19,680 --> 05:34:23,600
>> THANK YOU.

6556
05:34:23,600 --> 05:34:24,200
DR. ZHAO.

6557
05:34:24,200 --> 05:34:25,720
>> I WOULD AGREE WITH THAT AND

6558
05:34:25,720 --> 05:34:29,120
IN OUR CLINICAL TRIALS WE ALWAYS

6559
05:34:29,120 --> 05:34:31,760
COLLECT SAMPLES OVER TIME.

6560
05:34:31,760 --> 05:34:33,840
AVENUE SOME TRIALS ARE WELL

6561
05:34:33,840 --> 05:34:35,600
FIVELY SMALL SAMPLE SIZE.

6562
05:34:35,600 --> 05:34:38,440
SOME ARE LARGE.

6563
05:34:38,440 --> 05:34:40,800
AND WHILE BASICALLY IT DEPENDS

6564
05:34:40,800 --> 05:34:42,680
ON WHAT KIND OF METABOLITES

6565
05:34:42,680 --> 05:35:00,680
YOU'RE TALKING ABOUT.

6566
05:35:00,680 --> 05:35:02,320
YOU WILL BE ABLE TO SEE

6567
05:35:02,320 --> 05:35:04,240
SIGNIFICANT CHANGES OVER TWO OR

6568
05:35:04,240 --> 05:35:06,000
THREE MONTHS TIME BUT IF YOU'RE

6569
05:35:06,000 --> 05:35:09,200
TALKING ABOUT OTHER METABOLITES

6570
05:35:09,200 --> 05:35:10,640
MAYBE A WEAK SIGNAL AND THE

6571
05:35:10,640 --> 05:35:12,960
PRODUCER IS A MINOR MEMBER OF

6572
05:35:12,960 --> 05:35:15,720
THE COMMUNITY THEN YOU MAY NEED

6573
05:35:15,720 --> 05:35:17,240
RATHER LARGE SAMPLE SIZE TO BE

6574
05:35:17,240 --> 05:35:22,080
ABLE TO DETECT THAT.

6575
05:35:22,080 --> 05:35:24,360
>> GOOD POINT.

6576
05:35:24,360 --> 05:35:28,040
>> THE ONE OTHER THING I WOULD

6577
05:35:28,040 --> 05:35:31,240
ADD IS THAT -- IT'S VERY EASY

6578
05:35:31,240 --> 05:35:34,120
FOR US WHO STUDY THE MICROBIOME

6579
05:35:34,120 --> 05:35:37,440
TO THINK ABOUT THE MICROBIOME AS

6580
05:35:37,440 --> 05:35:39,320
THE ACTOR ACTING ON THE HOST.

6581
05:35:39,320 --> 05:35:44,240
AND AND A LOT OF TIMES WHEN WE

6582
05:35:44,240 --> 05:35:46,040
WHEN I TALK TO THE CLINICAL

6583
05:35:46,040 --> 05:35:50,640
FELLOWS AND THEY ASK ME WHY ARE

6584
05:35:50,640 --> 05:35:54,040
MICROBIOMES IMPORTANT.

6585
05:35:54,040 --> 05:35:56,520
REALLY THE BACTERIA DON'T EVEN

6586
05:35:56,520 --> 05:35:58,480
KNOW THE HOST EXIST.

6587
05:35:58,480 --> 05:36:01,680
THEY JUST KNOW THAT THEIR --

6588
05:36:01,680 --> 05:36:02,120
EXIST.

6589
05:36:02,120 --> 05:36:03,880
AND IT'S THE HOST THAT IS

6590
05:36:03,880 --> 05:36:05,440
INTERPRETING THE SIGNALS OF

6591
05:36:05,440 --> 05:36:06,520
THESE BACTERIA.

6592
05:36:06,520 --> 05:36:10,560
SO WE'RE PRETTY CONVINCED THAT

6593
05:36:10,560 --> 05:36:14,360
FOR EXAMPLE BILE ACIDS -- ARE

6594
05:36:14,360 --> 05:36:15,280
BASICALLY SAYING SOMETHING ABOUT

6595
05:36:15,280 --> 05:36:17,000
THE NUTRITIONAL VALUE OF WHAT

6596
05:36:17,000 --> 05:36:19,200
THE HOST IS CONSUMING.

6597
05:36:19,200 --> 05:36:23,920
WHETHER THERE IS -- IN THIS CASE

6598
05:36:23,920 --> 05:36:30,680
PARTICULAR FATTY AS I FAT --
FATTY ACIDS I
N

6599
05:36:30,680 --> 05:36:32,800
THE DIET.

6600
05:36:32,800 --> 05:36:34,760
WHY IS THE HOST EVEN CARE ABOUT

6601
05:36:34,760 --> 05:36:36,440
THESE SMALL METABOLITES BEING

6602
05:36:36,440 --> 05:36:37,440
PRESENT.

6603
05:36:37,440 --> 05:36:39,640
AND WHY WOULD IT HAVE SYSTEMS IN

6604
05:36:39,640 --> 05:36:42,560
PLACE TO DETECT THESE THINGS.

6605
05:36:42,560 --> 05:36:47,640
AND I THINK THAT THAT HAS REALLY

6606
05:36:47,640 --> 05:36:48,760
HELPED US UNDERSTAND OR FRAME

6607
05:36:48,760 --> 05:36:51,080
SOME OF THE EXPERIMENTS TO

6608
05:36:51,080 --> 05:36:52,000
BETTER UNDERSTAND THE

6609
05:36:52,000 --> 05:36:53,520
RELATIONSHIP.

6610
05:36:53,520 --> 05:36:57,360
BUT & ALSO HAS GIVEN US A NEW

6611
05:36:57,360 --> 05:36:59,240
APPRECIATION OF BILE ACIDS BUT

6612
05:36:59,240 --> 05:37:01,320
WHEN WE FIRST STARTED OFF IT WAS

6613
05:37:01,320 --> 05:37:03,120
LIKE SEARCHING FOR THE KEYS

6614
05:37:03,120 --> 05:37:04,440
UNDER THE LIGHT.

6615
05:37:04,440 --> 05:37:06,720
IT'S EASY TO KNOW.

6616
05:37:06,720 --> 05:37:10,600
IT'S EASY TO STUDY FATTY ACIDS

6617
05:37:10,600 --> 05:37:11,920
BECAUSE YOU KNOW THEY ARE FROM

6618
05:37:11,920 --> 05:37:14,840
THE BACTERIA RATHER THAN THE

6619
05:37:14,840 --> 05:37:16,360
HOST.

6620
05:37:16,360 --> 05:37:20,640
WE NEED TO TAKE A STEP BACK AND

6621
05:37:20,640 --> 05:37:23,760
THINK ABOUT WHY DO THEY CARE

6622
05:37:23,760 --> 05:37:24,960
THAT THESE SPECIFIC MOLECULES

6623
05:37:24,960 --> 05:37:26,560
ARE PRESENT.

6624
05:37:26,560 --> 05:37:29,840
>> EXCELLENT OBSERVATION.

6625
05:37:29,840 --> 05:37:36,800
>> SO I DON'T WANT TO -- GIVE --

6626
05:37:36,800 --> 05:37:41,000
ANSWER BUT OVER-ALL WE DON'T

6627
05:37:41,000 --> 05:37:41,840
KNOW ENOUGH.

6628
05:37:41,840 --> 05:37:47,200
IN ORDER TO DO THESE STUDIES TO

6629
05:37:47,200 --> 05:37:49,960
SAY WHICH METABOLITE PROVIDES A

6630
05:37:49,960 --> 05:37:52,400
HEALTH BENEFIT -- AND A GOOD

6631
05:37:52,400 --> 05:37:55,280
CORRELATION -- WE NEED TO DO

6632
05:37:55,280 --> 05:38:01,480
MORE STUDIES.

6633
05:38:01,480 --> 05:38:06,920
WE NOW KNOW THAT -- CAN CONTROL

6634
05:38:06,920 --> 05:38:13,520
-- -- -- ---BUT BY A LARGE AND

6635
05:38:13,520 --> 05:38:16,200
WE JUST -- HAVE SCRATCHED THE

6636
05:38:16,200 --> 05:38:16,640
SURFACE.

6637
05:38:16,640 --> 05:38:20,280
WE FIRST NEED TO KNOW -- --

6638
05:38:20,280 --> 05:38:21,880
IMPORTANT PLAYERS.

6639
05:38:21,880 --> 05:38:29,520
THEN WE CAN REALLY -- MEANINGFUL

6640
05:38:29,520 --> 05:38:30,280
COMPARISON.

6641
05:38:30,280 --> 05:38:31,720
JUST MY TWO CENTS.

6642
05:38:31,720 --> 05:38:34,040
BUT MORE STUDIES NEED TO BE

6643
05:38:34,040 --> 05:38:35,600
DONE.

6644
05:38:35,600 --> 05:38:44,200
>> THANK YOU.

6645
05:38:44,200 --> 05:38:44,840
>> BACK TO THE ORIGINAL

6646
05:38:44,840 --> 05:38:50,880
QUESTION.

6647
05:38:50,880 --> 05:38:52,880
IT'S DIFFICULT TO TELL THE

6648
05:38:52,880 --> 05:38:56,240
SAMPLE SIZE BECAUSE THE IDEA OF

6649
05:38:56,240 --> 05:38:58,320
DEVELOPING THE SAMPLE SIZE WE

6650
05:38:58,320 --> 05:39:00,120
KNOW ALL OF THE THINGS THAT

6651
05:39:00,120 --> 05:39:03,200
AFFECT THE METABOLITE AND THE

6652
05:39:03,200 --> 05:39:05,080
SMALL MOLECULE THAT THEY ARE

6653
05:39:05,080 --> 05:39:07,520
LOOKING AT BUT IT DEPENDS ON THE

6654
05:39:07,520 --> 05:39:09,440
COHORT CHARACTERISTICS.

6655
05:39:09,440 --> 05:39:11,840
A POPULATION FROM THE SAME AREA

6656
05:39:11,840 --> 05:39:14,680
THAT MIGHT BE YOU NEED A SMALLER

6657
05:39:14,680 --> 05:39:17,880
NUMBER BUT IF YOU INCREASE THE

6658
05:39:17,880 --> 05:39:20,320
GEOGRAPHIC REACH OF THE STUDY

6659
05:39:20,320 --> 05:39:24,080
AND THAT IS -- JUST LOOK AT --

6660
05:39:24,080 --> 05:39:27,280
STUDIES -- INCREASING THE NUMBER

6661
05:39:27,280 --> 05:39:30,200
SO YOU HAVE MORE VARIABILITY.

6662
05:39:30,200 --> 05:39:32,120
WE KNOW WHAT THE VARIABILITY OF

6663
05:39:32,120 --> 05:39:34,400
THE METABOLITE WAS THEN WE COULD

6664
05:39:34,400 --> 05:39:36,720
COME UP WITH A MORE REASONABLE

6665
05:39:36,720 --> 05:39:37,480
SAMPLE SIZE.

6666
05:39:37,480 --> 05:39:40,160
BUT IF YOU'RE DOING A DISCOVERY

6667
05:39:40,160 --> 05:39:42,920
STUDY I DON'T THINK YOU WOULD BE

6668
05:39:42,920 --> 05:39:46,600
ABLE TO DO THAT.

6669
05:39:46,600 --> 05:39:50,120
IN THE MIDWEST EVERYBODY PRETTY

6670
05:39:50,120 --> 05:39:52,640
MUCH EATS THE SAME THING.

6671
05:39:52,640 --> 05:39:55,000
IF WE DID THE SAME THING

6672
05:39:55,000 --> 05:39:58,320
COMPARED TO THE -- THE WEST

6673
05:39:58,320 --> 05:40:00,200
COAST THERE WOULD BE A HUGE

6674
05:40:00,200 --> 05:40:02,280
DIFFERENCE IN DIETARY FIBER AND

6675
05:40:02,280 --> 05:40:04,280
THAT IS WHAT DROVE US TO DO SOME

6676
05:40:04,280 --> 05:40:06,040
OF THESE STUDIES.

6677
05:40:06,040 --> 05:40:08,640
IF WE EXPANDED OUR GROUP WE

6678
05:40:08,640 --> 05:40:10,280
WOULD HAVE LOST SOME OF THE

6679
05:40:10,280 --> 05:40:12,160
SIGNALS WE WERE SEEING BECAUSE

6680
05:40:12,160 --> 05:40:14,600
THERE WAS SO MUCH BASE LINE

6681
05:40:14,600 --> 05:40:15,400
VARIABILITY.

6682
05:40:15,400 --> 05:40:17,360
THE TWO LARGE STUDIES THAT HAVE

6683
05:40:17,360 --> 05:40:20,440
LOOKED AT THIS -- WHICH IS THOSE

6684
05:40:20,440 --> 05:40:27,520
LOOKING AT THE GUY -- GLYCEMIC

6685
05:40:27,520 --> 05:40:28,360
RESPONSE.

6686
05:40:28,360 --> 05:40:31,400
AND THEY WERE DONE ACROSS TWO

6687
05:40:31,400 --> 05:40:31,680
CONTINENTS.

6688
05:40:31,680 --> 05:40:33,600
IT'S ALL PART OF THE DEVELOPED

6689
05:40:33,600 --> 05:40:34,680
WORLD.

6690
05:40:34,680 --> 05:40:36,920
NOT TAKING -- THE DEVELOPING

6691
05:40:36,920 --> 05:40:37,880
WORLD.

6692
05:40:37,880 --> 05:40:39,080
SO I IMAGINE IF YOU WANTED TO

6693
05:40:39,080 --> 05:40:41,240
LOOK AT THE SAME IN THE

6694
05:40:41,240 --> 05:40:43,160
DEVELOPING WORLD IT WOULD TAKE A

6695
05:40:43,160 --> 05:40:45,600
SIMILAR COHORT SIZE TO FIND THE

6696
05:40:45,600 --> 05:40:47,400
SAME INDICATORS.

6697
05:40:47,400 --> 05:40:48,160
>> ALL RIGHT.

6698
05:40:48,160 --> 05:40:52,040
AND I'LL JUST ADD THAT WHEN WE

6699
05:40:52,040 --> 05:40:55,520
WERE PUTTING TOGETHER OUR WORK

6700
05:40:55,520 --> 05:40:58,560
-- FOR OUR PROGRAM WE STRUGGLED

6701
05:40:58,560 --> 05:41:02,520
WITH THESE SAME ISSUES AND THE

6702
05:41:02,520 --> 05:41:05,920
SOLUTION IS SOMETHING LIKE AN --

6703
05:41:05,920 --> 05:41:07,840
TRIAL OR DO YOU DISCOVERY

6704
05:41:07,840 --> 05:41:09,960
SCIENCE AND THEN FIGURE OUT THE

6705
05:41:09,960 --> 05:41:11,840
VARIATION IS AND DO IT IN A

6706
05:41:11,840 --> 05:41:13,080
SMALLER COHORT.

6707
05:41:13,080 --> 05:41:16,440
IT'S A HUGE ISSUE THAT EVERYONE

6708
05:41:16,440 --> 05:41:20,840
IS TRYING TO TACKLE.

6709
05:41:20,840 --> 05:41:21,360
DR. ZHAO

6710
05:41:21,360 --> 05:41:24,400
>> -- THE SAMPLE SIZE QUESTION,

6711
05:41:24,400 --> 05:41:26,360
OF COURSE HOST IS THE RESPONSE.

6712
05:41:26,360 --> 05:41:29,080
AFFECTS THE RESPONSE.

6713
05:41:29,080 --> 05:41:30,520
IS ACTUALLY CRITICAL.

6714
05:41:30,520 --> 05:41:33,680
AND SO WE NEED TO KNOW HOW MUCH

6715
05:41:33,680 --> 05:41:39,240
OF THE MICRO -- PRODUCT -- AND

6716
05:41:39,240 --> 05:41:43,200
THAT CAN ACTUALLY INDUCE A

6717
05:41:43,200 --> 05:41:48,040
RESPONSE -- WHICH CAN BE

6718
05:41:48,040 --> 05:41:48,680
MEASURED.

6719
05:41:48,680 --> 05:41:52,440
WE WOULD LIKE TO SEE A

6720
05:41:52,440 --> 05:41:54,400
DIFFERENCE -- BETWEEN THE TWO

6721
05:41:54,400 --> 05:41:57,040
DIFFERENT GROUPS AND THAT IS

6722
05:41:57,040 --> 05:41:59,040
CRITICAL FOR ESTIMATING SAMPLE

6723
05:41:59,040 --> 05:42:01,600
SIZE.

6724
05:42:01,600 --> 05:42:03,920
AND I WOULD LIKE TO ADD A SHORT

6725
05:42:03,920 --> 05:42:04,880
COMMENT ON THE PREVIOUS

6726
05:42:04,880 --> 05:42:05,560
QUESTION.

6727
05:42:05,560 --> 05:42:09,640
OF VIABILITY OF PRO-BIOTIC

6728
05:42:09,640 --> 05:42:10,200
BACTERIA.

6729
05:42:10,200 --> 05:42:17,480
THE PRODUCT PUTTING BENEFICIAL

6730
05:42:17,480 --> 05:42:19,040
-- ARE HIGHLY AVAILABLE.

6731
05:42:19,040 --> 05:42:22,760
THEY ARE SO READILY -- ABSORBED.

6732
05:42:22,760 --> 05:42:25,960
HOWEVER THEY ARE PRODUCERS IF

6733
05:42:25,960 --> 05:42:29,160
NOT HAVING ECOLOGICAL DOMINANCE

6734
05:42:29,160 --> 05:42:32,360
IN THE GUT THEN THE ACTUAL

6735
05:42:32,360 --> 05:42:35,520
PRODUCTS PRODUCED IT WOULD BE

6736
05:42:35,520 --> 05:42:41,400
LIMITED SO THE HOST ACTUALLY

6737
05:42:41,400 --> 05:42:48,600
BECOMES DEFICIENT.

6738
05:42:48,600 --> 05:42:51,280
WE MAY NEED TO INTRODUCE ANOTHER

6739
05:42:51,280 --> 05:42:55,320
CONCEPT -- FOR PRO-BIOTIC

6740
05:42:55,320 --> 05:42:58,560
BACTERIA.

6741
05:42:58,560 --> 05:43:00,760
>> INTERESTING.

6742
05:43:00,760 --> 05:43:03,280
SO DR. -- I'M GOING TO MOVE TO A

6743
05:43:03,280 --> 05:43:05,160
QUESTION THAT HAS BEEN BURNING.

6744
05:43:05,160 --> 05:43:07,400
IT LOOKS LIKE FOUR PEOPLE HAVE

6745
05:43:07,400 --> 05:43:08,280
ASKED THIS.

6746
05:43:08,280 --> 05:43:10,880
THIS IS ABOUT TRANSIT TIME.

6747
05:43:10,880 --> 05:43:19,640
THIS IS FOR DR. KASHYAP.

6748
05:43:19,640 --> 05:43:22,520
HOW IMPORTANT IS TRANSIT TIME

6749
05:43:22,520 --> 05:43:24,960
KNOWING THAT HUMANS ARE ABLE TO

6750
05:43:24,960 --> 05:43:27,240
CONTROL THEIR TRANSIT TIME AND

6751
05:43:27,240 --> 05:43:32,160
CHOOSE WHEN TO DEFECATE.

6752
05:43:32,160 --> 05:43:34,960
AND HOW MUCH OVERLAP IS THERE

6753
05:43:34,960 --> 05:43:36,960
BETWEEN MICE TRANSIT TIME VERSUS

6754
05:43:36,960 --> 05:43:38,400
HUMAN KNOWING THEY ARE VERY

6755
05:43:38,400 --> 05:43:41,520
DIFFERENT.

6756
05:43:41,520 --> 05:43:43,360
>> I CAN TAKE THE SECOND ONE IF

6757
05:43:43,360 --> 05:43:51,680
YOU WANT TO TAKE THE FIRST ONE.

6758
05:43:51,680 --> 05:43:55,760
>> SO THE SECOND PART -- MICE

6759
05:43:55,760 --> 05:43:59,240
DEFECATE -- IT'S NOT HARD TO GET

6760
05:43:59,240 --> 05:44:03,160
24 HOUR STOOL --S FROM THEM

6761
05:44:03,160 --> 05:44:05,440
ESPECIALLY DURING THEIR FEEDING

6762
05:44:05,440 --> 05:44:06,040
TIME.

6763
05:44:06,040 --> 05:44:08,040
MORE PELLETS THAN WE KNOW WHAT

6764
05:44:08,040 --> 05:44:09,800
TO DO W THERE IS ALWAYS A

6765
05:44:09,800 --> 05:44:16,920
QUESTION OF WHETHER THESE

6766
05:44:16,920 --> 05:44:17,840
CIRCADIAN CHANGES THAT WE

6767
05:44:17,840 --> 05:44:20,680
OBSERVE IN MICE APPLY TO HUMANS.

6768
05:44:20,680 --> 05:44:23,880
WE KNOW THAT HUMAN ORAL SAMPLES

6769
05:44:23,880 --> 05:44:28,480
LIKE SALIVA AND SKIN DO HAVE

6770
05:44:28,480 --> 05:44:29,960
CIRCADIAN FLUCTUATION AND THERE

6771
05:44:29,960 --> 05:44:32,960
WAS A RECENT PAPER BY THE GROUP

6772
05:44:32,960 --> 05:44:39,320
IN GERMANY -- WHO SHOWED THAT

6773
05:44:39,320 --> 05:44:42,280
THERE IS CIRCADIAN TO THE

6774
05:44:42,280 --> 05:44:44,040
MICROBIOME WHEN LOOKED AT A

6775
05:44:44,040 --> 05:44:45,640
POPULATION LEVEL MEANING THAT

6776
05:44:45,640 --> 05:44:48,960
PEOPLE WHO TEND TO DEFECATE

6777
05:44:48,960 --> 05:44:50,920
LATER IN THE DAY HAVE A

6778
05:44:50,920 --> 05:44:54,360
DIFFERENT MICROBIOME COMPOSITION

6779
05:44:54,360 --> 05:44:56,080
THAN THOSE WHO DEFECATE EARLIER

6780
05:44:56,080 --> 05:44:57,000
IN THE DAY.

6781
05:44:57,000 --> 05:44:59,200
WE HAVE DONE SOME PRELIMINARY

6782
05:44:59,200 --> 05:45:02,960
LOOK AT THE AMERICAN GUT AND

6783
05:45:02,960 --> 05:45:06,240
OPEN BIOME SETS AND WHAT WE

6784
05:45:06,240 --> 05:45:08,840
FOUND IS WHEN YOU LOOK -- OPEN

6785
05:45:08,840 --> 05:45:10,400
BIOME HAS INDIVIDUALS WHO HAVE

6786
05:45:10,400 --> 05:45:13,040
PROVIDED HUNDREDS OF STOOL

6787
05:45:13,040 --> 05:45:15,560
SAMPLES AND COLLECTED USUALLY

6788
05:45:15,560 --> 05:45:17,240
BETWEEN 9 AND 5.

6789
05:45:17,240 --> 05:45:18,840
WHAT WE'VE FOUND IS THAT THERE

6790
05:45:18,840 --> 05:45:21,280
IS NO WAY TO PREDICT WHEN A

6791
05:45:21,280 --> 05:45:24,680
SAMPLE WAS COLLECTED BASED ON

6792
05:45:24,680 --> 05:45:28,680
THIS COMPOSITION.

6793
05:45:28,680 --> 05:45:31,800
EITHER WITHIN ONE INDIVIDUAL OR

6794
05:45:31,800 --> 05:45:33,320
CROSS INDIVIDUALS.

6795
05:45:33,320 --> 05:45:37,240
THESE CYCLICAL CHANGES SEEM TO

6796
05:45:37,240 --> 05:45:39,840
EXIST IN A MORE POPULATION LEVEL

6797
05:45:39,840 --> 05:45:41,520
AS OPPOSED TO AN INDIVIDUAL

6798
05:45:41,520 --> 05:45:42,840
LEVEL THAT YOU HAVE TO HAVE

6799
05:45:42,840 --> 05:45:44,640
THOUSANDS OF SAMPLINGS TO

6800
05:45:44,640 --> 05:45:47,200
ACTUALLY BE ABLE TO SEE THESE

6801
05:45:47,200 --> 05:45:50,440
FLUCTUATIONS.

6802
05:45:50,440 --> 05:45:53,040
SO THEN COMES THE IMPORTANT AND

6803
05:45:53,040 --> 05:45:55,320
ANOTHER IMPORTANT QUESTION.

6804
05:45:55,320 --> 05:45:56,840
USUALLY WE HAVE -- MOST PEOPLE

6805
05:45:56,840 --> 05:45:59,720
HAVE A RECTUM IN WHICH WE STORE

6806
05:45:59,720 --> 05:46:02,040
OUR POOP UNTIL IT IS SOCIALLY

6807
05:46:02,040 --> 05:46:04,680
APPROPRIATE TO DEFECATE.

6808
05:46:04,680 --> 05:46:08,640
AND THAT WHILE IT IS THERE WATER

6809
05:46:08,640 --> 05:46:10,840
IS BEING ABSORBED BY THE COLON

6810
05:46:10,840 --> 05:46:13,400
AND THE NATURE OF THE EVENTER IS

6811
05:46:13,400 --> 05:46:15,640
CHANGING AND PROMOTING CERTAIN

6812
05:46:15,640 --> 05:46:17,240
BACTERIA AND WHAT NOT.

6813
05:46:17,240 --> 05:46:19,360
THE ONE THING THAT WE STRUGGLE

6814
05:46:19,360 --> 05:46:22,160
WITH -- WITH HUMAN RESEARCH IS

6815
05:46:22,160 --> 05:46:24,480
WHETHER THE BIOME IS INDICATIVE

6816
05:46:24,480 --> 05:46:26,440
OF WHAT WAS GOING ON IN OTHER

6817
05:46:26,440 --> 05:46:28,640
REGIONS THAT ARE MORE

6818
05:46:28,640 --> 05:46:29,400
BIOLOGICALLY IMPORTANT.

6819
05:46:29,400 --> 05:46:34,920
IN THE ILEUM OR IN A PATIENT

6820
05:46:34,920 --> 05:46:39,000
WITH INFLAMMATORY BOWEL DISEASE

6821
05:46:39,000 --> 05:46:42,840
-- WHETHER THEY ARE INDICATIVE

6822
05:46:42,840 --> 05:46:45,720
OF SOME OF THE OTHER REGIONS AND

6823
05:46:45,720 --> 05:46:47,560
WE ARE STRUGGLING TO FIND THAT

6824
05:46:47,560 --> 05:46:48,560
IT IS.

6825
05:46:48,560 --> 05:46:51,560
AND SOME SAMPLES THAT WE'VE

6826
05:46:51,560 --> 05:46:53,560
LOOKED AT WE'RE NOT FINDING THAT

6827
05:46:53,560 --> 05:46:55,440
SORT OF SIGNATURE AND THAT IS

6828
05:46:55,440 --> 05:46:58,240
WHY THE STOOL HAS NOT BEEN THAT

6829
05:46:58,240 --> 05:47:02,160
GREAT OF A BIOMARKER.

6830
05:47:02,160 --> 05:47:03,920
SO I THINK THERE NEEDS TO BE

6831
05:47:03,920 --> 05:47:09,080
BETTER WAYS OF ASSESSING THE

6832
05:47:09,080 --> 05:47:11,960
MICROBIOME BESIDES STOOL.

6833
05:47:11,960 --> 05:47:14,680
AND AS WAS SUGGESTED EARLIER

6834
05:47:14,680 --> 05:47:16,600
MAYBE EARLIER METHODS SUCH AS

6835
05:47:16,600 --> 05:47:19,040
LOOKING AT BLOOD OR URINE OR

6836
05:47:19,040 --> 05:47:19,680
SOMETHING ELSE.

6837
05:47:19,680 --> 05:47:23,040
BUT I THINK THAT WE DEFINITELY

6838
05:47:23,040 --> 05:47:24,880
NEED TO BETTER UNDERSTAND WHAT

6839
05:47:24,880 --> 05:47:27,160
IS IT THAT WE'RE LOOKING AT WHEN

6840
05:47:27,160 --> 05:47:29,920
WE'RE LOOKING AT STOOL

6841
05:47:29,920 --> 05:47:32,000
MICROBIOME FROM HUMANS.

6842
05:47:32,000 --> 05:47:34,040
S IT STORAGE TIME.

6843
05:47:34,040 --> 05:47:37,840
IS IT A REFLECTION OF DIET?

6844
05:47:37,840 --> 05:47:40,640
OR -- WHAT I THINK IS GOING ON

6845
05:47:40,640 --> 05:47:43,040
IS ALL OF THOSE THINGS ARE

6846
05:47:43,040 --> 05:47:44,960
DROWNING OUT OF THE ORGANISMS

6847
05:47:44,960 --> 05:47:47,240
AND METABOLITES THAT ARE PERHAPS

6848
05:47:47,240 --> 05:47:48,720
MORE IN PARTICULARRIVE OF WHAT

6849
05:47:48,720 --> 05:47:52,040
IS GOING ON PHYSIOLOGICALLY AND

6850
05:47:52,040 --> 05:47:53,600
WE NEED TO FIGURE OUT HOW TO

6851
05:47:53,600 --> 05:47:54,840
SEPARATE THE NOISE FROM THE

6852
05:47:54,840 --> 05:47:57,040
SIGNAL.

6853
05:47:57,040 --> 05:48:00,040
>> THANK YOU.

6854
05:48:00,040 --> 05:48:02,920
>> I THINK ONE THING TO REMEMBER

6855
05:48:02,920 --> 05:48:07,480
IS THAT PEOPLE GO BACK AND FORTH

6856
05:48:07,480 --> 05:48:09,160
AND THERE ARE FUNDAMENTAL

6857
05:48:09,160 --> 05:48:11,280
DIFFERENCES AND WE CANNOT CROSS

6858
05:48:11,280 --> 05:48:13,840
COMPARE TRANSIT TIMES BETWEEN

6859
05:48:13,840 --> 05:48:15,440
THE TWO.

6860
05:48:15,440 --> 05:48:19,640
MICE WILL DEFECATE WHEN THEY --

6861
05:48:19,640 --> 05:48:22,560
-- AND HUMANS -- THAT IS NOT HOW

6862
05:48:22,560 --> 05:48:25,440
WE MEASURE TRANSIT TIME.

6863
05:48:25,440 --> 05:48:26,960
IT'S GOING TO BE A VERY

6864
05:48:26,960 --> 05:48:30,240
DIFFERENT STUDY IN HUMANS AS

6865
05:48:30,240 --> 05:48:32,440
COMPARED TO MICE.

6866
05:48:32,440 --> 05:48:34,440
WE DON'T COLLECT HUMAN SAMPLES

6867
05:48:34,440 --> 05:48:38,280
AND PUT THEM IN LIQUID NITROGEN

6868
05:48:38,280 --> 05:48:40,800
RIGHT AWAY AS WE DO FOR MOUSE

6869
05:48:40,800 --> 05:48:41,040
SAMPLES.

6870
05:48:41,040 --> 05:48:43,240
THAT IS WHY YOU NEED A LARGER

6871
05:48:43,240 --> 05:48:47,320
POPULATION OF HUMANS WHEN YOU'RE

6872
05:48:47,320 --> 05:48:49,000
STUDYING THESE DIFFERENT

6873
05:48:49,000 --> 05:48:49,400
CHANGES.

6874
05:48:49,400 --> 05:48:52,040
THERE IS BOTH HUMAN STUDIES AND

6875
05:48:52,040 --> 05:48:53,640
ANIMAL STUDIES WHICH SHOW THAT

6876
05:48:53,640 --> 05:48:56,840
THE TRANSIT TIME IMPACTS THE

6877
05:48:56,840 --> 05:48:59,160
MICROBIOME COMPOSITION AND

6878
05:48:59,160 --> 05:49:02,520
VISA-VERSA.

6879
05:49:02,520 --> 05:49:07,520
WE HAD DONE A STUDY -- TRYING TO

6880
05:49:07,520 --> 05:49:10,600
SEE IF THIS IS MUTUALLY

6881
05:49:10,600 --> 05:49:14,880
REINFORCING FORMULA WHERE IF IT

6882
05:49:14,880 --> 05:49:16,040
CHANGES IF YOU TAKE THAT

6883
05:49:16,040 --> 05:49:19,200
COMMUNITY AND PUT THEM INTO A

6884
05:49:19,200 --> 05:49:21,960
BRAND-NEW HEALTHY MOUSE WILL YOU

6885
05:49:21,960 --> 05:49:24,080
PERPETUATE THAT PHENOTYPE AND

6886
05:49:24,080 --> 05:49:27,440
YOU DO TO SOME EXTENT.

6887
05:49:27,440 --> 05:49:30,640
WHICH MEANS IF THE MICROBES ARE

6888
05:49:30,640 --> 05:49:33,240
DRIVING -- IT DOESN'T MATTER HOW

6889
05:49:33,240 --> 05:49:35,240
THEY CAME TO BE THERE.

6890
05:49:35,240 --> 05:49:37,400
WHETHER THEY WERE INITIALLY

6891
05:49:37,400 --> 05:49:39,160
SELECTED BECAUSE THE PATIENT WAS

6892
05:49:39,160 --> 05:49:41,560
CONSTIPATED OR BECAUSE THE MOUSE

6893
05:49:41,560 --> 05:49:42,880
WAS CONSTIPATED BUT IT'S GOING

6894
05:49:42,880 --> 05:49:46,280
TO TRY TO PERPETUATE THAT

6895
05:49:46,280 --> 05:49:48,320
PHENOTYPE IN THE HOST.

6896
05:49:48,320 --> 05:49:51,480
AND THAT WAS SORT OF ONE STUDY

6897
05:49:51,480 --> 05:49:54,680
THAT WE DID TO TRY TO UNDERSTAND

6898
05:49:54,680 --> 05:49:56,360
THIS DIFFERENCE BETWEEN CAUSE

6899
05:49:56,360 --> 05:49:58,120
AND EFFECT WHICH IS WHAT WE

6900
05:49:58,120 --> 05:49:59,640
FOCUS ON.

6901
05:49:59,640 --> 05:50:01,320
THE MINE CORRECTS DO THE CAUSE

6902
05:50:01,320 --> 05:50:02,240
AND EFFECT.

6903
05:50:02,240 --> 05:50:05,280
OR IS IT A MUTUALLY ENFORCING

6904
05:50:05,280 --> 05:50:07,200
MECHANISM AND THIS EXISTS IN

6905
05:50:07,200 --> 05:50:08,720
MOST PHENOTYPES.

6906
05:50:08,720 --> 05:50:10,920
CHRONIC INFLAMMATION, IT DOESN'T

6907
05:50:10,920 --> 05:50:13,080
HAVE TO BE THE -- EVENT.

6908
05:50:13,080 --> 05:50:14,840
BUT ONCE THE COMMUNITY IS

6909
05:50:14,840 --> 05:50:16,560
ESTABLISHED IN AN INFLAMED GUT

6910
05:50:16,560 --> 05:50:18,960
IT'S GOING TO TRY TO PERPETUATE

6911
05:50:18,960 --> 05:50:42,880
THAT PHENOTYPE.

6912
05:50:42,880 --> 05:50:44,800
I THINK YOU CAN ASSESS THE FACT

6913
05:50:44,800 --> 05:50:47,760
OF TRANSIT ON THE MICROBIOME.

6914
05:50:47,760 --> 05:50:50,440
THE OTHER DIFFERENCE -- IN TERMS

6915
05:50:50,440 --> 05:50:52,560
OF WHAT DOES THE STOOL

6916
05:50:52,560 --> 05:50:53,200
REPRESENT?

6917
05:50:53,200 --> 05:50:56,840
WHEN WE TAKE MOUSE SAMPLES -- IT

6918
05:50:56,840 --> 05:50:58,200
GIVES YOU ALL OF THE INFORMATION

6919
05:50:58,200 --> 05:50:59,040
FROM THE STOOL.

6920
05:50:59,040 --> 05:51:02,880
FROM HUMAN SCHOOLS -- ONE THE

6921
05:51:02,880 --> 05:51:07,880
CONSISTENCY VARIES.

6922
05:51:07,880 --> 05:51:11,840
-- ---THE FACT THAT IT'S NOT

6923
05:51:11,840 --> 05:51:16,200
UNIFORM ACROSS THE ENTIRE

6924
05:51:16,200 --> 05:51:18,680
SURFACE OF THE STOOL.

6925
05:51:18,680 --> 05:51:20,280
-- THEREOF HAVE BEEN STUDIES

6926
05:51:20,280 --> 05:51:23,120
EARLY ON LOOKING AT CORE SAMPLES

6927
05:51:23,120 --> 05:51:26,040
FROM A STOOL AS COMPARED -- TO

6928
05:51:26,040 --> 05:51:27,920
SEE IF THERE ARE DIFFERENCES.

6929
05:51:27,920 --> 05:51:31,240
THERE ARE DIFFERENCES IN THE

6930
05:51:31,240 --> 05:51:33,720
METABOLITES AND IN THE MICROBES.

6931
05:51:33,720 --> 05:51:37,920
HOW DOES THIS LEAD TO ACTUAL

6932
05:51:37,920 --> 05:51:39,680
BIAS IN THE FINDINGS AND IF IT

6933
05:51:39,680 --> 05:51:41,600
DOES LEAD TO A BIAS IN THE

6934
05:51:41,600 --> 05:51:44,200
FINDINGS.

6935
05:51:44,200 --> 05:51:46,280
TRANSIT TIME IS AN IMPORTANT

6936
05:51:46,280 --> 05:51:49,040
CONSIDERATION.

6937
05:51:49,040 --> 05:51:53,200
BECAUSE HUMANS TRANSIT TIME IS

6938
05:51:53,200 --> 05:51:57,040
UP TO 24 HOURS AS COMPARED TO

6939
05:51:57,040 --> 05:51:59,960
MICE YOU MIGHT NOT GET

6940
05:51:59,960 --> 05:52:01,600
EVERYTHING THAT YOU'RE LOOKING

6941
05:52:01,600 --> 05:52:02,240
FOR.

6942
05:52:02,240 --> 05:52:07,240
IF YOU LOOK AT A SAMPLE OF STOOL

6943
05:52:07,240 --> 05:52:08,760
THAT IS TAKEN AT ANY TIME AND

6944
05:52:08,760 --> 05:52:12,280
COMPARE IT TO A 48 HOUR SAMPLE

6945
05:52:12,280 --> 05:52:17,560
STOOL -- STORING THE FAT AND

6946
05:52:17,560 --> 05:52:21,120
CALCULATING -- IT'S SENSITIVE --

6947
05:52:21,120 --> 05:52:22,760
IT'S NOT PERFECT BUT IT'S NOT

6948
05:52:22,760 --> 05:52:25,040
TERRIBLE EITHER.

6949
05:52:25,040 --> 05:52:26,040
SO THERE IS DEFINITELY

6950
05:52:26,040 --> 05:52:27,680
ADVANTAGES AND THAT IS WHY WE

6951
05:52:27,680 --> 05:52:29,760
LOOK AT A 48 HOUR COLLECTION

6952
05:52:29,760 --> 05:52:34,200
WHEN WE LOOK AT SOME OF THE

6953
05:52:34,200 --> 05:52:35,040
MARKERS.

6954
05:52:35,040 --> 05:52:36,480
WE'RE NOT THERE IN MATERIALS OF

6955
05:52:36,480 --> 05:52:38,040
GETTING THERE FOR THE

6956
05:52:38,040 --> 05:52:38,640
MICROBIOME.

6957
05:52:38,640 --> 05:52:47,160
IT'S GOING TO TAKE TIME.

6958
05:52:47,160 --> 05:52:48,040
>> SURE.

6959
05:52:48,040 --> 05:52:48,880
THAT MAKES SENSE.

6960
05:52:48,880 --> 05:52:54,240
WE'RE GOING TO GO TO DR. KIM.

6961
05:52:54,240 --> 05:52:58,880
>> MY QUESTION IS VERY SPECIFIC

6962
05:52:58,880 --> 05:53:04,360
TO -- ---I HAVE A QUESTION

6963
05:53:04,360 --> 05:53:07,360
AROUND EXPANDING YOUR RESEARCH

6964
05:53:07,360 --> 05:53:10,040
CONCEPT ON THE -- FOR EXAMPLE

6965
05:53:10,040 --> 05:53:16,040
MANY OF THE PERSONS WHO --

6966
05:53:16,040 --> 05:53:18,480
CONSUME THE PRO-BIOTICS IN THE

6967
05:53:18,480 --> 05:53:20,360
HUMAN POPULATION.

6968
05:53:20,360 --> 05:53:22,440
THEY OFTEN TIMES HAVE DIFFERENT

6969
05:53:22,440 --> 05:53:24,440
MEDICATIONS AND DO WE -- CUFF

6970
05:53:24,440 --> 05:53:27,000
COMMENT ON WHETHER THE RESEARCH

6971
05:53:27,000 --> 05:53:29,560
HAS BEEN DONE TO UNDERSTAND WHAT

6972
05:53:29,560 --> 05:53:32,640
WOULD BE THE AFFECT OF THE

6973
05:53:32,640 --> 05:53:33,160
PRO-BIOTICS.

6974
05:53:33,160 --> 05:53:36,200
8 OR IS IT THE OTHER WAY AROUND.

6975
05:53:36,200 --> 05:53:41,360
HOW THIS DRUG CREATES -- EFFECTS

6976
05:53:41,360 --> 05:53:45,560
-- ---OR HOW WE ARE AFFECTED BY

6977
05:53:45,560 --> 05:53:48,320
THE PRO-BIOTIC INTAKE DURING THE

6978
05:53:48,320 --> 05:53:49,840
DIFFERENT MEDICATION.

6979
05:53:49,840 --> 05:53:52,040
DO WE KNOW ABOUT THIS AND WHAT

6980
05:53:52,040 --> 05:53:55,240
IS THE BEST WAY TO INTERROGATE

6981
05:53:55,240 --> 05:53:56,640
THESE QUESTIONS.

6982
05:53:56,640 --> 05:53:58,760
>> THIS IS A WONDERFUL REALLY

6983
05:53:58,760 --> 05:54:00,280
GREAT QUESTION.

6984
05:54:00,280 --> 05:54:03,480
AND I THINK THAT I'LL GIVE TWO

6985
05:54:03,480 --> 05:54:06,440
ANSWERS.

6986
05:54:06,440 --> 05:54:14,520
SO IN -- WE SIMPLY DON'T KNOW

6987
05:54:14,520 --> 05:54:16,880
ABOUT THE ROLE OF THE MICROBIOME

6988
05:54:16,880 --> 05:54:20,080
AND DRUG METABOLISM IN HUMANS.

6989
05:54:20,080 --> 05:54:23,400
I REPEAT THE ESTIMATE OF MAYBE

6990
05:54:23,400 --> 05:54:28,000
BEING 30-40 YEARS BEHIND OF OUR

6991
05:54:28,000 --> 05:54:30,960
UNDERSTANDING OF DRUG

6992
05:54:30,960 --> 05:54:32,800
METABOLISM.

6993
05:54:32,800 --> 05:54:37,320
WE'RE NOW POISED TO START TO

6994
05:54:37,320 --> 05:54:41,280
STUDY THESE QUESTIONS AND I'LL

6995
05:54:41,280 --> 05:54:44,880
COME BACK TO THE MODELING.

6996
05:54:44,880 --> 05:54:46,880
MATHEMATIC MODELING TO TRY TO

6997
05:54:46,880 --> 05:54:48,000
MAKE PREDICTIONS ABOUT THINGS

6998
05:54:48,000 --> 05:54:49,800
THAT ARE HARD TO MEASURE

6999
05:54:49,800 --> 05:54:50,560
DIRECTLY.

7000
05:54:50,560 --> 05:54:52,000
SO FOR EXAMPLE IT MAY BE

7001
05:54:52,000 --> 05:54:53,440
DIFFICULT TO SAY WHAT IS THE

7002
05:54:53,440 --> 05:54:56,960
IMPACT OF A CERTAIN PRO-BIOTIC

7003
05:54:56,960 --> 05:55:00,480
ON MICROBIOME MEDIATED DRUG

7004
05:55:00,480 --> 05:55:02,640
METABOLISM BUT WE COULD ASK

7005
05:55:02,640 --> 05:55:04,040
SOMETHING LIKE WHAT WOULD HAPPEN

7006
05:55:04,040 --> 05:55:08,440
IF THE NET ACTIVITY -- INCREASED

7007
05:55:08,440 --> 05:55:10,440
BY 20% OR 80%.

7008
05:55:10,440 --> 05:55:12,240
HOW MUCH WOULD THAT AFFECT THE

7009
05:55:12,240 --> 05:55:15,000
AMOUNT OF A TOXIC DRUG

7010
05:55:15,000 --> 05:55:16,840
METABOLITE EXPOSURE IN

7011
05:55:16,840 --> 05:55:17,640
CIRCULATION.

7012
05:55:17,640 --> 05:55:20,200
AND IF THE MODEL TELLS US THAT

7013
05:55:20,200 --> 05:55:23,040
EVEN A CHANGE OF 80% WOULD NOT

7014
05:55:23,040 --> 05:55:25,240
HAVE A VERY BIG EFFECT IN

7015
05:55:25,240 --> 05:55:27,240
CIRCULATION THEN WE FOCUS ON A

7016
05:55:27,240 --> 05:55:28,000
DIFFERENT TARGET.

7017
05:55:28,000 --> 05:55:29,840
SO I THINK IT'S GOING TO BE A

7018
05:55:29,840 --> 05:55:31,840
COMBINES OF USING MODELING TO

7019
05:55:31,840 --> 05:55:35,600
PREDICT WHAT THE MOST TRACTABLE

7020
05:55:35,600 --> 05:55:39,840
DRUGS AND MICROBES WILL BE AS

7021
05:55:39,840 --> 05:55:41,600
WELL AS DOING THE STUDIES.

7022
05:55:41,600 --> 05:55:43,320
THE REASON WE GOT INTERESTED IN

7023
05:55:43,320 --> 05:55:47,600
THE FIRST PLACE IS THIS IS A

7024
05:55:47,600 --> 05:55:49,560
PROTOBASE TO THE MICROBIOME THAT

7025
05:55:49,560 --> 05:55:51,040
YOU CAN PREDICT.

7026
05:55:51,040 --> 05:55:52,640
IT'S DIFFICULT TO PREDICT WHEN

7027
05:55:52,640 --> 05:55:56,360
SOMEONE WILL GET CANCER OR IDB.

7028
05:55:56,360 --> 05:55:59,000
BUT WE CAN PREDICT WHEN SOMEONE

7029
05:55:59,000 --> 05:56:01,440
WILL TAKE A DRUG.

7030
05:56:01,440 --> 05:56:03,200
THIS IS AN OPPORTUNITY TO LOOK

7031
05:56:03,200 --> 05:56:05,720
AND ASK HOW WELL WE CAN

7032
05:56:05,720 --> 05:56:06,680
UNDERSTAND WHAT ARE HAPPENS

7033
05:56:06,680 --> 05:56:08,720
AFTER THE DRUG IS CONSUMED.

7034
05:56:08,720 --> 05:56:11,200
SO THOSE ARE NOT VERY SATISFYING

7035
05:56:11,200 --> 05:56:13,120
ANSWERS BUT YOU RAISED SOME VERY

7036
05:56:13,120 --> 05:56:14,840
IMPORTANT QUESTIONS.

7037
05:56:14,840 --> 05:56:15,840
>> EXCELLENT.

7038
05:56:15,840 --> 05:56:17,280
KATHERINE IF YOU DON'T MIND

7039
05:56:17,280 --> 05:56:20,520
PUTTING UP THE SLIDE ON THE OVER

7040
05:56:20,520 --> 05:56:21,600
ARCHING QUESTIONS.

7041
05:56:21,600 --> 05:56:24,240
WHILE YOU ARE THINKING ABOUT THE

7042
05:56:24,240 --> 05:56:25,800
ANSWERS TO THESE LITTLE

7043
05:56:25,800 --> 05:56:27,760
QUESTIONS -- WHICH ARE HUGE I

7044
05:56:27,760 --> 05:56:29,280
JUST WANT TO REFLECT ON THE FACT

7045
05:56:29,280 --> 05:56:33,160
THAT I THINK GOING BACK TO

7046
05:56:33,160 --> 05:56:35,240
DR. DONOVAN'S COMMENTS HOW IT

7047
05:56:35,240 --> 05:56:37,320
WOULD BE NICE TO HAVE SOME

7048
05:56:37,320 --> 05:56:38,640
GUIDELINES FOR RESEARCH.

7049
05:56:38,640 --> 05:56:40,680
COMMON DATA ELEMENTS.

7050
05:56:40,680 --> 05:56:42,560
WAYS TO COLLECT SAMPLES.

7051
05:56:42,560 --> 05:56:42,960
ETC.

7052
05:56:42,960 --> 05:56:44,720
IT SOUNDS LIKE THIS GROUP AND

7053
05:56:44,720 --> 05:56:46,520
THE REST OF THE SPEAKERS IN THE

7054
05:56:46,520 --> 05:56:49,040
WORKSHOP MIGHT BE THE GROUP TO

7055
05:56:49,040 --> 05:56:49,800
HELP SET THAT.

7056
05:56:49,800 --> 05:56:52,040
I WANT TO PLANT THAT AS A SEED

7057
05:56:52,040 --> 05:56:54,840
THAT YOU GUYS ARE THE PEOPLE AND

7058
05:56:54,840 --> 05:56:58,280
THAT I'VE BEEN SO IMPRESSED WITH

7059
05:56:58,280 --> 05:56:59,640
EVERYTHING THAT YOU'VE TALKED

7060
05:56:59,640 --> 05:57:00,040
ABOUT.

7061
05:57:00,040 --> 05:57:03,040
THIS COULD BE A POTENTIAL

7062
05:57:03,040 --> 05:57:07,280
PRODUCT OF THE WORKSHOP.

7063
05:57:07,280 --> 05:57:11,840
I WILL BE QUIET AND LET YOU SEE

7064
05:57:11,840 --> 05:57:13,600
IF THERE IS ANYTHING YOU WANT TO

7065
05:57:13,600 --> 05:57:15,960
TALK ABOUT.

7066
05:57:15,960 --> 05:57:20,000
>> I THINK STANDARDIZATION IS

7067
05:57:20,000 --> 05:57:22,080
KEY FOR SUCCESS AND FOR US TO

7068
05:57:22,080 --> 05:57:25,120
COMPARE OUR NOTES AND INTEGRATE

7069
05:57:25,120 --> 05:57:27,240
OUR DATA AND CONFIRM THE

7070
05:57:27,240 --> 05:57:27,680
FINDINGS.

7071
05:57:27,680 --> 05:57:31,000
I HAVE BEEN WORKING WITH

7072
05:57:31,000 --> 05:57:36,720
INTERNATIONAL HUMAN MICROBIOME

7073
05:57:36,720 --> 05:57:38,120
CONSORTIUM.

7074
05:57:38,120 --> 05:57:44,920
AND ONE CONTINUOUS EFFORT TO IS

7075
05:57:44,920 --> 05:57:46,160
TO DEVELOP QUALITY CONTROL

7076
05:57:46,160 --> 05:57:47,760
STANDARDS

7077
05:57:47,760 --> 05:57:51,280
EVERYBODY MUST USE THE SAME --

7078
05:57:51,280 --> 05:57:53,000
-- THAT IS NOT THE RIGHT WAY TO

7079
05:57:53,000 --> 05:57:53,960
GO.

7080
05:57:53,960 --> 05:57:57,240
BUT HOWEVER WE NEED TO SET A

7081
05:57:57,240 --> 05:57:58,040
STANDARD.

7082
05:57:58,040 --> 05:58:00,200
WHAT KIND OF RECOVERY RATE AND

7083
05:58:00,200 --> 05:58:04,880
HOW TO ENSURE ALL OF THE CELLS

7084
05:58:04,880 --> 05:58:09,880
-- -- -- AND THAT KIND OF

7085
05:58:09,880 --> 05:58:11,280
STANDARD NEEDS TO BE DISCUSSED

7086
05:58:11,280 --> 05:58:13,240
AND ESTABLISHED AND AGREED BY

7087
05:58:13,240 --> 05:58:15,320
EVERYBODY IN THE FIELD SO THAT

7088
05:58:15,320 --> 05:58:19,760
WE CAN COMPARE OUR NOTES.

7089
05:58:19,760 --> 05:58:31,800
>> EXCELLENT POINT.

7090
05:58:31,800 --> 05:58:35,720
>> ONE -- WHICH HAS BEEN HELPFUL

7091
05:58:35,720 --> 05:58:38,280
IS THE IMMENSE EFFORT THAT WENT

7092
05:58:38,280 --> 05:58:41,480
INTO ALL OF US WHICH IS

7093
05:58:41,480 --> 05:58:44,600
COLLECTING EVERY SINGLE SAMPLE

7094
05:58:44,600 --> 05:58:47,400
-- AND THERE WAS A HUGE MISSED

7095
05:58:47,400 --> 05:58:48,400
OPPORTUNITY WHERE THAT IS THE

7096
05:58:48,400 --> 05:58:50,640
KIND OF STUDIES THAT COULD HAVE

7097
05:58:50,640 --> 05:58:51,680
HELPED.

7098
05:58:51,680 --> 05:58:54,880
STANDARDIZED AND IMPLEMENTED AND

7099
05:58:54,880 --> 05:58:59,640
-- AND I THINK -- TO SET UP

7100
05:58:59,640 --> 05:59:01,080
SOMETHING LIKE THAT AGAIN IS NOT

7101
05:59:01,080 --> 05:59:03,360
GOING TO BE FEASIBLE.

7102
05:59:03,360 --> 05:59:07,440
BUT -- WOULD COLLECT STOOL

7103
05:59:07,440 --> 05:59:09,840
SAMPLES -- FROM A LARGE PORTION.

7104
05:59:09,840 --> 05:59:13,280
AND IT WOULD BE HELPFUL AND

7105
05:59:13,280 --> 05:59:14,080
ESTABLISHING BASELINE

7106
05:59:14,080 --> 05:59:15,760
VARIABILITY IN A LOT OF THESE

7107
05:59:15,760 --> 05:59:17,520
FACTORS WHICH I THINK IS NEEDED.

7108
05:59:17,520 --> 05:59:20,240
THE QUESTION IS HOW IS THE DATA

7109
05:59:20,240 --> 05:59:27,040
GOING TO BE USED BEYOND AS

7110
05:59:27,040 --> 05:59:29,120
OPPOSED TO -- SEEDING ADDITIONAL

7111
05:59:29,120 --> 05:59:32,400
STUDIES.

7112
05:59:32,400 --> 05:59:34,400
EVERYBODY IS DOING CLINICAL

7113
05:59:34,400 --> 05:59:36,840
STUDIES AND DOING ANIMAL

7114
05:59:36,840 --> 05:59:37,240
STUDIES.

7115
05:59:37,240 --> 05:59:39,240
THERE IS VERY LITTLE CARRASCO

7116
05:59:39,240 --> 05:59:40,920
MOON INDICATION BETWEEN THE TWO

7117
05:59:40,920 --> 05:59:43,440
REGIONS AND SO EVERYBODY COMES

7118
05:59:43,440 --> 05:59:47,080
UP WITH DIFFERENT HYPOTHESIS BUT

7119
05:59:47,080 --> 05:59:50,240
THEY ARE NOT CROSS FEEDING AS

7120
05:59:50,240 --> 05:59:52,480
MUCH AS WOULD HELP ADVANCE THE

7121
05:59:52,480 --> 05:59:52,920
FIELD.

7122
05:59:52,920 --> 05:59:55,520
I PUT UP THE LAST SLIDE.

7123
05:59:55,520 --> 05:59:58,080
IF YOU WORK CONCURRENTLY IN

7124
05:59:58,080 --> 05:59:58,760
DIFFERENT AREAS.

7125
05:59:58,760 --> 06:00:04,040
8 THAT WOULD REALLY HELP.

7126
06:00:04,040 --> 06:00:05,400
>> EXCELLENT.

7127
06:00:05,400 --> 06:00:05,640
THANK YOU.

7128
06:00:05,640 --> 06:00:08,280
7 I'LL OFFER THE OPPORTUNITY FOR

7129
06:00:08,280 --> 06:00:09,600
ONE LAST COMMENT AND THEN TURN

7130
06:00:09,600 --> 06:00:10,720
IT OVER TO THE ORGANIZERS

7131
06:00:10,720 --> 06:00:16,600
>> I THINK I THROUGHOUT THE

7132
06:00:16,600 --> 06:00:18,040
TALKS I HEARD ABOUT HOW

7133
06:00:18,040 --> 06:00:21,440
IMPORTANT NUTRITION IS AND HOW

7134
06:00:21,440 --> 06:00:24,760
DIFFICULT IT IS TO MEASURE.

7135
06:00:24,760 --> 06:00:26,960
THE WEAKEST LINK BUT BUILDING ON

7136
06:00:26,960 --> 06:00:30,240
THE COMMENT I THINK WE'RE AT A

7137
06:00:30,240 --> 06:00:34,440
KEY TIME WITH NUTRITION FOR

7138
06:00:34,440 --> 06:00:37,160
PRECISION WHERE THERE IS SO MUCH

7139
06:00:37,160 --> 06:00:38,280
POTENTIAL OVERLAP.

7140
06:00:38,280 --> 06:00:40,040
A WHOLE CLINICAL CENTER THAT IS

7141
06:00:40,040 --> 06:00:43,040
GOING TO BE LOOKING AT COMPARING

7142
06:00:43,040 --> 06:00:48,360
THE ASA24 AND DEVELOPING NOVEL

7143
06:00:48,360 --> 06:00:49,560
METHODS.

7144
06:00:49,560 --> 06:00:52,240
GETTING THAT CROSS TALK BETWEEN

7145
06:00:52,240 --> 06:00:54,400
-- WITH THE NUTRITION FOR

7146
06:00:54,400 --> 06:00:55,880
PRECISION HEALTH.

7147
06:00:55,880 --> 06:00:58,920
ROB NIGHTS LAB -- GOT THE

7148
06:00:58,920 --> 06:01:01,600
SEQUENCING THE MICROBIOME CENTER

7149
06:01:01,600 --> 06:01:04,680
AND SO THEY CAN CERTAINLY BE IN

7150
06:01:04,680 --> 06:01:07,160
THOSE CONVERSATIONS OF HOW DO WE

7151
06:01:07,160 --> 06:01:08,400
STANDARDIZE AND COLLECT THE

7152
06:01:08,400 --> 06:01:10,040
SAMPLES AND GETTING INTO THE

7153
06:01:10,040 --> 06:01:11,760
OTHER SAMPLES WHICH ARE GOING TO

7154
06:01:11,760 --> 06:01:16,560
BE CRITICALLY IMPORTANT FOR

7155
06:01:16,560 --> 06:01:18,640
UNDERSTANDING THE METABOLISM.

7156
06:01:18,640 --> 06:01:20,800
WE REALLY NEED TO BRING THESE

7157
06:01:20,800 --> 06:01:24,040
TOGETHER.

7158
06:01:24,040 --> 06:01:24,560
>> SLEPT.

7159
06:01:24,560 --> 06:01:28,120
THANK YOU.

7160
06:01:28,120 --> 06:01:29,640
-- EXCELLENT.

7161
06:01:29,640 --> 06:01:31,080
THE MORE CONVERSATIONS WE CAN

7162
06:01:31,080 --> 06:01:34,120
HAVE THE CLOSER WE'LL GET TO

7163
06:01:34,120 --> 06:01:35,320
STANDARDIZATION.

7164
06:01:35,320 --> 06:01:36,720
>> IF PEOPLE KEEP THROWING UP

7165
06:01:36,720 --> 06:01:38,120
THEIR HANDS SAYING IT'S TOO

7166
06:01:38,120 --> 06:01:38,920
HARD.

7167
06:01:38,920 --> 06:01:42,320
WE DON'T KNOW HOW TO MEASURE: 

7168
06:01:42,320 --> 06:01:45,040
WE'RE GOING TO FUND YOU GUYS TO

7169
06:01:45,040 --> 06:01:46,840
FIGURE OUT HOW TO DO THIS.

7170
06:01:46,840 --> 06:01:49,840
THAT IS TWO COMPLETELY DIFFERENT

7171
06:01:49,840 --> 06:01:52,200
APPROACHES AND WE NEED SERIOUS

7172
06:01:52,200 --> 06:01:54,560
FUNDING IF NUTRITION IS

7173
06:01:54,560 --> 06:01:56,400
IMPORTANT FOR THESE DISEASES AND

7174
06:01:56,400 --> 06:01:57,680
THE MICROBIOME.

7175
06:01:57,680 --> 06:01:59,320
WE NEED TO FIGURE THIS OUT.

7176
06:01:59,320 --> 06:02:01,640
IT SHOULD NOT BE ROCKET SCIENCE

7177
06:02:01,640 --> 06:02:03,200
>> GREAT POINT.

7178
06:02:03,200 --> 06:02:04,560
THANK YOU.

7179
06:02:04,560 --> 06:02:08,920
7 THANK YOU ALL FOR THE

7180
06:02:08,920 --> 06:02:09,920
WONDERFUL CONVERSATION.

7181
06:02:09,920 --> 06:02:11,920
THANK YOU ALL FOR YOUR WONDERFUL

7182
06:02:11,920 --> 06:02:12,120
TALKS.

7183
06:02:12,120 --> 06:02:14,120
YOU HAVE HIT ALL OF THE HIGH

7184
06:02:14,120 --> 06:02:15,840
POINTS.

7185
06:02:15,840 --> 06:02:24,440
ALL OF THE DIFFICULT TOPIC --S.

7186
06:02:24,440 --> 06:02:27,960
>> THANK YOU SO MUCH DR. VARGAS

7187
06:02:27,960 --> 06:02:30,960
AND HAMILTON AND ALL OF OUR

7188
06:02:30,960 --> 06:02:32,840
MODERATORS AND PRESENTERS TODAY.

7189
06:02:32,840 --> 06:02:35,240
THIS WAS A WONDERFUL DAY ONE.

7190
06:02:35,240 --> 06:02:41,840
I HAVE TH TASK OF DRAWING DAY
ONE

7191
06:02:41,840 --> 06:02:42,680
TO A CONCLUSION.

7192
06:02:42,680 --> 06:02:44,600
I WANT TO REMIND OUR VIEWERS

7193
06:02:44,600 --> 06:02:47,320
THAT WE'RE HERE TOMORROW FOR DAY

7194
06:02:47,320 --> 06:02:49,640
TWO.

7195
06:02:49,640 --> 06:02:51,200
APRIL 27th AT 10:00 A.M.

7196
06:02:51,200 --> 06:02:53,440
EASTERN AND AGAIN WE'RE ON NIH

7197
06:02:53,440 --> 06:02:54,240
VIDEO CAST.

7198
06:02:54,240 --> 06:02:56,360
COME BACK AND JOIN US.

7199
06:02:56,360 --> 06:02:58,040
WE'RE SURE TO HAVE SOME

7200
06:02:58,040 --> 06:03:01,040
WONDERFUL TALKS AND SESSIONS

7201
06:03:01,040 --> 06:03:03,560
TOMORROW AND THEN DR. KIM AND

7202
06:03:03,560 --> 06:03:05,440
DR. -- WILL HAVE A FEW CLOSING

7203
06:03:05,440 --> 06:03:08,440
THOUGHTS AND WE LOOK FORWARD TO

7204
06:03:08,440 --> 06:03:12,320
HEARING FROM DR. GARY WOO AS OUR

7205
06:03:12,320 --> 06:03:13,440
KEYNOTE.

7206
06:03:13,440 --> 06:03:15,280
WITH THAT I'M GOING TO DRAW THIS

7207
06:03:15,280 --> 06:03:16,400
TO A CLOSE.

7208
06:03:16,400 --> 06:03:17,280
THANK YOU ALL.

7209
06:03:17,280 --> 06:03:19,040
I WISH EVERYBODY A LOVELY

7210
06:03:19,040 --> 06:03:21,040
EVENING AND WE'LL SEE YOU ALL

7211
06:03:21,040 --> 06:03:21,480
TOMORROW.

7212
06:03:21,480 --> 06:03:22,160
THANK YOU EVERYONE AND HAVE A

7213
06:03:22,160 --> 06:04:21,400
GREAT EVENING.