NEXT WEEK WE HAVE ANOTHER PROGRAM ON NEGLECTED DISEASES. WE TALK ABOUT MANY DISEASES HERE WITH A HUGE NUMBER OF PEOPLE INVOLVED, HIV AND SEVERAL OTHERS, TUBERCULOSIS BUT THERE ARE DISEASES, QUITE A FEW THAT, AFFECT MILLIONS AND MILLIONS AROUND THE WORLD AND THEY SORT OF COME UNDER THE RADAR. I DON'T THINK MANY SCIENTISTS AREN'T AWARE OF THE GREAT NEGLECTED DISEASES. AND IT MEANS THERE'S A TREMENDOUS OPPORTUNITY FOR IMAGINATIVE RESEARCH. IT'S NOT THAT THERE AREN'T GOOD INTELLIGENT CREATIVE PEOPLE WORKING ON THESE DISEASES BUT IT NEEDS THE KIND OF BRIDGING SUCH AS ILLUSTRATED IN OUR LOGO FOR THOSE WHO DON'T KNOW THAT'S THE OAKLAND BRIDGE AND YOU ARE LIKE THE GENTLEMEN ON THE CATWALK LINKING AN EXCITING AREA OF BASIC SCIENCE WITH THE BROOKLYN SIDE WITH THE IMPACT ON HEALTH. WE'LL GET TO THAT. THE FOLLOWING WEEK WE HAVE A UNIQUE OPPORTUNITY THE CREATOR OF THE TELESCOPE AT NASA AND RECEIVED A NOBEL PRIZE FOR THE COBY STUDY OF THE FORMATION OF THE UNIVERSE. THE BIG BANG ANALYSIS AND HE'LL TALK ABOUT COSMIC IMAGING. AND WE'LL HAVE A TALK ON IMAGING AT THE MOLECULAR LEVEL. IT SHOULD BE INTERESTING. I JUST WANT TO SAY A COUPLE WORDS. SO THIS IS THE BASIS FOR THE DISCOVERY OF THE INNATE IMMUNE SYSTEM. AND THERE WAS A STUDY OF LIVING THINGS WITH THE MICROSCOPE OF THE DAY. THIS IS MID 19th CENTURY. SIMPLE MICROSCOPE. WHAT HE OBSERVED WAS WHEN THEY LOOKED AT THE LARVAE OF A STAR FISH HE COULD SEE CELLS THAT WERE COMING IN TO REPAIR THE WOUND. AND HE BELIEVED THE MACROPHAGES WERE A RESPONSE AND HE SHARED THE NOBEL PRIZE IN 1908 FOR THIS. NOW, TYPICAL IN SCIENCE AND I BRING THIS UP BECAUSE IT'S VERY RELEVANT TODAY. AND WE'VE ALL LEARNED THERE'S VERY LITTLE A TO B IN BIOLOGICAL SCIENCES. THERE'S TOO MANY Cs, Ds, F AND THE WHOLE THING IS A NETWORK BUT WE BELIEVE IN OUR A TO B AND SOMEBODY ELSE BELIEVES IN THEIR C TO D AND YOU NEED A BRIDGE TO GET PEOPLE TO TALK TOGETHER SO HE DISCOVERED PHAGOCYTOSIS AND THERE WERE OTHERS BY REPUTATION WITH A GROUP OF FELLOWS AND SO FORTH WHO DISAGREED AND THEY INSISTED THAT SERUM, ANTIBODY WAS THE KEY. THAT WAS THE WAY. AND THIS WAS A WHOLE EXPLOSIVE AREA WHICH ULTIMATELY LED TO THE DISCOVERY OF T CELL AND B CELLS. AND THEY'VE WIDELY BEEN RECOGNIZED AS THE FATHER OF IMMUNITY. >> SO HE GOT INVOLVED IN THE STUDY OF AGING IN THE EARLY 20th VINCH -- CENTURY AND A DON'T KNOW HOW HE ACTUALLY GOT INTO THE FACT THAT THE GUT BACTERIA WERE LIKE A SEPARATE POPULATION IN OUR BODY AND THAT THEY WERE REALLY IMPORTANT IN HEALTH AND DISEASE. AND HE FOUND, AND BELIEVES IF HE COULD REPLACE THOSE BACTERIA WITH LACTIC ACID FORMING ONE LIKE THE ONES USED IN YOGURT. HE WAS IMPRESSED THERE WERE A LOT OF VERY OLD PEOPLE WHO WERE OLD, HE THOUGHT, BECAUSE THEY'D BEEN EATING YOGURT AND WHEN HE DIED AT ABOUT THE AGE OF 65, I THINK, HIS BIGGEST DISTRESS WAS HIS OPPONENTS WOULD SAY, HMM, SEE WHAT THAT YOGURT DID FOR YOU. YOU DIDN'T MAKE IT BEYOND 65. BUT HE HAD ANOTHER BIG IDEA. DO SOME BACTERIA PRODUCE DISEASE OR GUT BACK TETERIA THROUGH PRODUCING TOXINS AND CREATED THE IDEA OF AUTOINTOXICATION WHICH IS TODAY'S WORLD. IT LED TO THE IDEA OF WHETHER YOU CAN REPLACE THE GUT BACTERIA AND PREVENT DISEASE AND HE SPECULATED THAT MAYBE IT COULD EVEN DELAY AGING. THIS WAS SORT OF THE FIRST PRO-BIOTIC. AND HE BECAME KNOWN AS IF YOU EAT YOGURT YOU'LL LIVE TO BE 90. AT ANY WAY, HE WAS WAY AHEAD OF THE PACK. AND WE'RE VERY DELIGHT TO HAVE TWO COLLEAGUES AT NIH WHO ARE ALSO VERY MUCH INVOLVED AND I WOULD SAY RIGHT UP THERE WITH THE PACK. OUR FIRST SPEAKER IS -- WHO I SHOULD HAVE MENTIONED, HE ENDED HIS CAREER BY BEING THE PASTOR OF THE INSTITUTE WHERE YASMINE GOT HER Ph.D. SORT OF LIKE HANDING THE TORCH. THERE SHE STUDIED AND IMMUNE RESPONSES IN THE INNATE SYSTEM AND THE CONTINUED HER WORK IN THE IMMUNE SYSTEM AND RELATIONSHIP TO THE GUT BACTERIA AND BEGAN TO STUDY GERM-FREE ANIMALS. THIS WAS A MAJOR BREAKTHROUGH AND HAS LED TO EXTRAORDINARY FINDINGS. SHE CAME TO THE NIH AND CONTINUED OUR OUTSTANDING RESEARCH AND HER HONORS WOULD KEEP US HERE FOR A LONG TIME BUT SHE WAS ELECT TO THE NATIONAL ACADEMY OF SCIENCE AND LAST YEAR AND WE'RE DELIGHTED SHE'S WITH US TODAY AND WILL TELL US WHERE WE STAND. AND WE HAVE A KEY INVESTIGATOR IN THE AUTOIMMUNE LIVER DISEASE BRANCH. SHE GRADUATED IN MEDICINE IN GERMANY BUT INTERESTED IN IMMUNOLOGY AND SPENT A PRODUCTIVE TERM AT THE SCRIPPS INSTITUTE. SHE'S BEEN ONE OF THE LEADERS IN THE DEVELOPMENT OF UNDERSTANDING OF THE IMMUNOLOGY RELATED TO VIRAL ININFECTION INFECTION OF THE LIVER AND THAT'S AN AREA SHE'S CONTINUE TO WORK. IN ADDITION, SHE HAS AN EXTRAORDINARY PAPER THAT WAS PUBLISH PUBLISHED A COUPLE MONTHS AGO WHICH I'M SURE MANY PEOPLE -- I ENJOYED READING IMMENSELY AND I USUALLY CAN'T GET THROUGH MANY PAPERS BUT DISCOVERED THE MICROB MICROBUY BIOME MICROBIOME DIFFERENCES AND WHAT HAPPENS WHEN YOU CHANGE THE STRAINS IN RELATIONSHIP TO IMMUNE RESPONSES. SO ENOUGH OF INTRODUCTION. I'LL TRY TO GIVE A BIG OVERVIEW OF SOME OF THE MAIN INFORMATION OF THE RELATIONSHIP IN THE MACROBIOTA. SO OF COURSE THIS IS I SLIDE YOU'VE SEEN MANY TIMES WE'RE COMPOSED OF CELLS AND THIS IS ALL SURFACES AND THIS IS HIGHLY DIVERSE AND BELIEVED TO BE AS NUMEROUS AS THE CELLS IN THE BODY AND THE NUMBER OF CELLS EXPRESS READY LIKELY HIGHER THAN OUR OWN IMMUNE SYSTEM. IT'S NOT A NEW FINDING WE'RE pAND SOMEONE WHO HAS A NAME I CANNOT PRONOUNCE, I WAS ABLE TO SHOW THE DISCOVERY OF THE FIRST PRIMITIVE MICROSCOPE AND I THINK THIS IMAGE IS WHAT HE DREW AS MENTIONED EARLIER WHAT HE BELIEVED IS IT WAS TOXIC AND NEED TO REPLACE IT. HE SAW IT AS THE POTENTIAL ENEMY. AND THIS UNCOVERED THE HEALTH OF THE VAGINAL ECO SYSTEM AND WAS THE FIRST TO SHOW THE COLONIZATION RESISTANCE AND THE CLASSIC MICROBE CAN PREVENT COLONIZATION AGAINST PATHOGENS AND TODAY THIS IS THE BASIS OF A LARGE NUMBER OF EXPLORATION AND APPROACHES. SO A LARGE SUMMARY AFTER 15 YEARS OF WORK IT'S BEEN LINKED DIRECTLY AND INDIRECTLY. SO OF COURSE IT PLAYS A FUNDAMENTAL ROLE. AND THERE'S BEEN FASCINATING WORK EARLIER ON WITH THESE ANIMALS OR INDIVIDUALS TO TRANSFER METABOLIC SYNDROME WHICH IS REMARKABLE. THERE'S AN EMERGING LINE OF EVIDENCE LINKING THE BEHAVIOR AND FUNCTION TO THE EARLY LIFE TO POTENTIALLY LEAD TO DISORDERS AND THEY PLAY A FUNDAMENTAL ROLE OF THE HOST AND THEY ARE LOCAL AND SYSTEMIC. AND PART OF WHAT I'M GOING TO DISCUSS IS THE RELATIONSHIP OF THE MICROBE WITH THE IMMUNE SYSTEM. THE WORK THAT WAS DONE BY MANY GROUPS IS HIGHLIGHTING THE FUNDAMENTAL ROLE OF THE MICROBES. AND IT DIDN'T PLAY A ROLE IN DIFFERENT ASPECT. FIRST, THEY DIDN'T LEAD TO THE IMMUNE SYSTEM AND WE NEEDED IT TO BE PROPERLY BLOCKED. IT INFLUENCES THE QUALITY AND NUMBER OF CELLS AND THE FUNCTION HAS BEEN SHOWN AND I'LL DISCUSS SOME OF THE MECHANISMS LATER TO SHOW THE RESPONSE TO PATHOGENS AND PROTECTION FROM THE PATHOGEN AND THE FUNCTIONAL TUNING WHICH MEANS IN THE TISSUE I WILL INTRODUCE LOCAL FACTORS THAT HAVE THE CAPACITY TO IMPACT THE CELL ENTERING THE ISSUE AND IT'S IMPORTANT TO RECEIVE THE SIGNALS OF THE CYTOKINES THAT ARE IMPORTANT FOR CONTROLLING AND A LARGER AMOUNT OF WORK HAVE SHOWN THE CONTROL INFECTION AND IT'S BASED ON EVIDENT AND IT CAN PROMOTE THE VACCINE AND IMPORTANTLY THERE'S RESEARCH IT'S BEEN LINKED TO THE SUCCESS OF CONTROL OF CANCER AND IT WAS DONE BY A GROUP AND IT PROMOTED THE CONTROL OF TUMORS AND RECENTLY THIS WAS A DEVELOPMENT FOR OTHER GROUPS IN THE CONTEXT OF THE CONTEXT OF CANCER. A LARGE AMOUNT OF RESEARCH IS TO TRY TO UNDERSTAND THE MECHANISM BY WHICH IT CAN BOOST THE RESPONSE TO CANCER AND HOW THE DIFFERENCES CAN EXPLAIN DIFFERENCES IN RESPONSE TO TREATMENT. AND THERE'S EVIDENCE ON THE DEVELOPMENT FOR RESPONSES. AS I MENTIONED BEFORE, THE OTHER SYSTEM AND OTHER FACTORS AND THEY'VE ALLOWED THE EARLY LIFE ENCOUNTER TO THE MICROBES TO SHOW ATROPHY. THERE WAS A STUDY IN CANADA LOOKING AT CHILDREN THAT RECEIVE ANTIBIOTIC TREATMENT AND SHOWED IT WAS ENHANCEMENT. SO IT LINKED THE MICROBUY -- MICROBIOTA AND ALL THE TISSUES THAT ARE THE PRIMARY SITE TARGETED ARE THE NATURAL HABITAT OF THE MICROBIOTA AND IT INFECTS AN INDIVIDUAL THAT IS COLONIZED BY THE MIGHT MICROBES. AND WHEN WE NEED TO THINK ABOUT THE MACROBIOTA COME BACK WE HAVE TO REMEMBER IT'S A PATHOGEN. IT CONTAINS SOME CAN BE ANTIBIOTIC RESISTANT MICROBES AND THEY'RE HELD IN CHECK WITHIN THE G.I. TRACK OF A PERSON BECAUSE OF THE ACTION OF THE MICRO BIOTA AND IT PREVENTS THE COLONIZATION BY THE MICROBES. SO IT'S IMPORTANT TO REMEMBER THAT THE MICROBUY MICROBIOTA IS COLONIZED. SO THE WORK DONE BY DIFFERENT INVESTIGATORS AND ONE MODE OF ACTION IS INDIRECT AND THE MICROBE CAN SHOW ACTIVITY THAT CAN LIMIT THE INFECTION. AND THE PRODUCT OF THE MICROBIOTA SHOWS THE ABILITY TO COLONIZE AND FINALLY THERE'S DIRECT EVIDENCE OF THE ACTION OF THE MICROBIOTA AND BECAUSE THEY CAN PREVENT COLONIZATION AND THERE'S COMPETITION FOR THE AMOUNT OF NUTRIENTS PRESENT AND WHEN THE [INDISCERNIBLE] IS LOW. AND THIS CAN THEN HAVE AN EFFECT. SO WE HAVE ALL THESE DIFFERENT ACTIVITIES PROVIDING A FUNDAMENTAL SHIELD TO PREVENT THE COLONIZATION OF A LARGE NUMBER OF PATHOGENS. THE RELATIONSHIP CAN BE EXEMPLIFIED AND SOME IN THE CLINICAL SETTINGS THEY CAN UNFORTUNATELY BE COLONIZED BY A PATHOGEN AND IT CAN LEAD TO DRAMATIC CONSEQUENCES. THIS LED DIFFERENT SCIENTISTS AND OTHERS TO DIFFERENT APPROACHES THAT TRY TO PREVENT THESE EXUBERANT GROWTH OF MICROBE AND THIS HAS AFFECTED THE TREATMENT AND IN 97% OF THE CASES BY A LIFE-THREATENING DISEASE CAN BE CONTROVERSITRANSFERRED BY THE MICROBES OF HEALTHY INDIVIDUALS AND THEY HAVE TRIED TO LOOK AT OTHER PATHOGENS AND IT'S NOW THE NEXT PHASE OF THE FIELD FOR THE TRANSFER AND TO UNDERSTAND IF IT'S THE BEST TRANSFER TO CONTROL INFECTION AND LOOKING AT CANCER THERAPY TO SEE IF A COCKTAIL CAN BOOST RESPONSE. SO THE MICROBIOTA PLAYS AN IMPORTANT ROLE AND THERE'S THE ABILITY TO HAVE CYTOKINES THAT HAVE THE ABILITY TO LOOK AT THE RESPONSES. AND IT LED TO AN UNDERSTANDING THAT THEY CAN BE CONTROLLED BY THE MICROBIOTA. IT CAN BE IT LOOKS AT THE ABILITY OF RESPONSES AND FINDLY SO THERE WAS A TALENTED TEAM WERE ABLE TO SHOW THE ABILITY OF THE CELLS TO PRODUCE IN THE GUT WAS SIGNIFICANTLY DECREASED AND IT WAS LINKED TO THE ENHANCED ABILITY OF THE MICROBE TO COLONIZE THE MICE. SO THE WORK LED TO AN INFORMATION OF THE GOOD MICROBIOTA AND WITH THE WORK OF DON LITMAN WE LOOKED AT THE ME MICROBE THAT COULD BE FOUND IN MICE AND WE LOOKED AT MICE FROM DIFFERENT FACILITIES AND WERE ABLE TO SHOW THEY ARE VASTLY DIFFERENT IN THEIR ABILITY TO CONTROL WITHIN THE EXAMPLE. THIS IS WHERE A DOUGH DE DEFINED CLASS OF MICROBE COULD SHOW A LARGE NUMBER OF DISEASE AND SOME AFFECTING THE GUT AND SOME THE LUNG. INFLUENZA HAS BEEN LINKED TO BE CONTROLLED BY THE QUALITY OF THE BACTERIA IN THE GUT. WHAT WE NEED TO REMEMBER IS THE MICROBUY O MICROBUY OWE B MICROBIOTA CAN HAVE AN EFFECT AND IN ANIMALS THAT COLONIZE NATURALLY AND THE ANIMAL IS BETTER ABLE TO CONTROL THE INFECTION AND BETTER ABLE TO CONTROL A CLASS OF TUMORS. IN CERTAIN CASES PROTASE MAY BE SUFFICIENT AND WORK DONE AT NYU SHOWED A VIRUS CAN BE SUFFICIENT IN SOME CASES TO PUSH THE SYSTEM AND MANY MICROBE CAN INCORPORATE THE ACTION OF ALL MICROBES FOR THE OPTIMAL CONTROL OF THE IMMUNE SYSTEM. WHAT WE NEED TO THINK ABOUT IS OTHER FORMS OF ORGANISMS PRESENT IN THE DIFFERENT TISSUE. SO I WANTED TO DISCUSS WITH YOU A VERY IMPORTANT POINT ABOUT THE NEGATIVE ROLE IN SOME CASES. IT HAS BEEN SHOWN IN THE G.I. TRACT THAT A CERTAIN CLASS OF PATHOGEN CAN BE PROMOTED BY THE ACTION OF THE MICROBIOTA. THIS WAS SHOWN IN THE CONTEXT OF ONE INFECTION AND THE EGGS IN THE G.I. TRACK -- TRACT ARE UNABLE TO HATCH AND IT NEEDS TO ENCOUNTER THE MOLECULES PRODUCED BY THE MICROBIOTA. AND IT HIGHLIGHTED THE GUT BIOTA AND FOR ALL VIRAL INFECTION THAT WAS REQUIRED FOR IT TO BE INFECTIOUS. IN SOME CASES INFECTIONS CAN BE PROMOTE THE MICROBIOTA. WORK THAT WAS DONE A FEW YEARS AGO REALLY HIGHLIGHTED THE IMPORTANCE OF THE SEPARATION BETWEEN THE STRUCTURES THAT IS IN THE GUT HERE IN BLUE AND THE BACTERIA IN THE CELL. IN MOST CASES ESPECIALLY IN THE G.I. TRACT THERE'S A SEPARATION BETWEEN THE TISSUE, THE GUT HERE AND THE MICROBE. THIS IS DUE TO THE STRUCTURE AND THE PEPTIDE AND ANTIBODY. AND WE CAN DO IT IN A WAY THAT IS CONTROLLED. INFECTION CHANGES THE RELATIONSHIP AND WITH AN ACUTE INFECTION THE SEPARATION FROM THE MICROBE THE SEPARATION IS NO LONGER SEE. YOU NO LONGER HAVE SEPARATION BETWEEN THE MICROBE AND IT'S ABLE TO INVADE THE ISSUE. MORE THAN THAT WITH ACUTE INFECTIONS IT CAN ESCAPE THE GUT AND THIS HAS BEEN REPORTED IN OTHER SYSTEMS IN THE CONTEXT OF AN EXPERIMENTAL MODEL BUT IN HIV THE TRANS LOCATION OF BACTERIA HAS NOW BEEN PROPOSED AS A MECHANISM TO ENHANCE INACTIVATION AND THE PROPAGATION OF THE VIRUS. SO THIS IS THE MICROBIOTA AND THE RESPONSES. AND ANOTHER THING THAT HAPPENED IN THE CONTEXT OF INFECTION THAT CAN THREATEN THE RELATIONSHIP IS THE COMPOSITION CAN CHANGE AND IT CAN THRIVE ON PRODUCT FROM THE PROCESS AND THIS IS THE CASE FOR BACTERIA THAT HAS BEEN DOMINANT IN THE CONTEXT OF AN INFECTION. HAVE YOU THE DOMINANCE OF THE G.I. TRACT AND E. COLI THAT IS RESPONSIBLE FOR THE PATHOLOGICAL RESPONSE. IN SOME INFECTION THE PATHOLOGY IS DUE TO THE MICROBE THAT CAN HOST DISEASE. IN SOME CASES IT CAN [INDISCERNIBLE] IN THE PROCESS. CLEARLY THERE SAY CLEAR ASSOCIATION WITH THE IMMUNE SYSTEM. WHAT IS LESS CLEAR IS YOU NEED TO LOOK AT HOW DIFFERENT THE CLASS OF IMMUNITY COULD BE FROM THE PATHOGEN. SO MOST OF WHAT WE KNOW OF HOW THE IMMUNE SYSTEM WORKS COMES FROM THE WORK WE HAVE DONE AS IMMUNOLOGISTS. AND THE CLASS OF IMMUNITY AND THE RESPONSE IS UNKNOWN. THAT'S SOMETHING WE'VE STARTED TO EM PLORE. -- EXPLORE AND THE TISSUE WE'VE ADDRESSED IS THE SKIN. IT'S COLONIZE IT'S OWN MICROBIOTA AND MANY HAVE HIGHLIGHTED THE ENVIRONMENT AND THESE MICROBES ARE PRESENT IN THE SURFACE AND IN THE STRUCTURES OF THE SKIN. AND IN THE TISSUE WE DECIDE TO EXPLORE THE TISSUE BECAUSE IT'S ACTUALLY LESS REACHED IN MICROBES. IT HAS A MORE DOMINANT EFFECT. AND WE START TO UNCOVER THE SKIN MICROBIOTA AND SHE WAS ABLE TO SHOW THE ABILITY TO CONTROL THE SYSTEMS WITH INDEPENDENT OF THE GUT MICROBIOTA AND DIFFERENT ENVIRONMENTS CAN CONTROL THE IMMUNE SYSTEM. AND THE GOAL IS TO SEE IF WE CAN UNCOVER A UNIQUE INTERACTION BETWEEN THE DIFFERENT CLASS OF MICROBE AND EXPLAINING THE MECHANISM USED BY THE IMMUNE SYSTEM. SO WE ACTUALLY TAKE THE MICROBES AND APPLY THEM TO THE SURFACE OF THE SKIN AND WE AT THE CLASS OF CELLS AS LONG AS LOOKING AT THE DIFFERENT CLASS OF MICROBES. THIS ALLOWED A DIFFERENT CLASS AND IT'S VERY MUCH IN LINE WITH THE WORK DONE ON THE G.I. TRACT AND IT HAS A SPECIFIC ABILITY TO ENGAGE IN THE IMMUNE SYSTEM AND WE FOUND IF YOU APPLY THE SKIN OF AN ANIMAL WITH A BACTERIA AND IN SOME CASES IT'S MICE WITH THEIR OWN MICROBIOTA YOU CAN LOOK AT THE CELLS IN THE SKIN AND WE ALL HAVE THESE MICROBES. WE WERE ABLE TO LOOK AT THE ABILITY TO ACTIVATE THE RESPONSE AND WHEN YOU WANT TO UNDERSTAND THE MICROBE OF THE SYSTEM YOU HAVE TO LOOK TO THE PLATE LEVEL AND IN SOME CASES THERE'S AN EXTREME LEVEL OF SOPHISTICATION IN THE ABILITY OF THE MICROBE TO ENGAGE IN THIS SYSTEM. SO WE WERE ABLE TO SHOW THE CELLS GENERATED IN RESPONSE TO THE ENCOUNTER WITH THE MICROBE ARE ABLE TO MIGRATE TO THE SKIN. THEY DO NOT CAUSE ANY INFLAMMATION WHICH SAY -- IS A STRIKING CELL AND THEY CAN PROMOTE THE PREDICTION AND THIS HAS CONSEQUENCES TO BLOCK THE ABILITY OF THE SPACE TO INFECT THE ANIMALS. TO SHOW THE RESPONSE LEADS TO THE GENERATION OF CELLS THAT CAN PROMOTE DEFENSE AGAINST PATHOGENS. CREATING PROTECTION AGAINST THE IN TENSION SO WE WERE ABLE TO SHOW CELLS GENERATED AGAINST THE PATHOGEN VERSUS OTHERS AND FOR THAT WE WERE ABLE STO TO LOOK AT GENE EXPRESSION AND THERE'S AN INITIAL SIGNATURE AND THEY EXPRESSED A LOT OF GENES LINKED WITH TISSUE REPAIR IN RESPONSE TO A PATHOGEN AND THEY WERE ABLE TO VISUALIZE THE CELLS WITH THE SKIN IN THE CONTEXT OF TISSUE INJURY. AND WE CAN SEE THE CELLS GENERATED AGAINST THE BACTERIA AND SHOWING THE CELLS AGAINST THE MICROBIOTA AND THIS IS THE ABILITY IN WHICH CAN EXPOSE THE PATHOGENS AND AT THE SAME TIME THIS LED TO THE POSSIBILITY THE CELLS MAY BE IMPORTANT FOR TISSUE REPAIR. AND THEY WERE ABLE TO PROMOTE THE REPAIR OF THE ANIMAL AND IT'S RESPONSE OF THE SIDE AND THE PROCESS THAT CAN BE ENHANCED AND IF THE ANIMAL DOES NOT HAVE THE CELL THE RESPONSE IS NO LONGER SEEN. IN SUMMARY THE CONTROLLING SYSTEM HAS MANY MECHANISM. SOME ARE DIRECT AND THIS IS THE ABILITY TO ENHANCE THE TISSUE AND THERE'S A COMPLEX PHENOMENA AND WHETHER THEY'RE INVADING THEY'RE CONSTANTLY PROBING THE SYSTEM AND SEEKING THE RESPONSE AND THIS PROCESS IS DISTINCT BECAUSE THERE'S NO INFLAMMATION AND THEY HAVE DEFENSES BUT IMPORTANTLY HAVE FLEXIBLE ABILITY TO PROMOTE PREPARE AND IT SHOWS US THE MICROBIOTA CAN LOOK AT THE PHYSIOLOGY OF THE TISSUE AND SO I THINK WE HAVE MUCH WORK TO DO TO UNDERSTAND HOW EACH MICROBE IS ABLE TO COMMUNICATE WITHIN THE SYSTEM AND BY TRYING TO UNDERSTAND THE RESPONSE TO THE INVADERS WE CAN BETTER UNDERSTAND HOW THE TISSUES ARE WIRED TO TRY TO UNDERSTAND HOW TO BOOST IMMUNITY AND THE MOLECULES PRODUCES BY THE MICROBES TO PROMOTE IT. AND THERE'S A LOT OF RESEARCH WHERE WE'LL UNDERSTAND THE MECHANISM THAT CAN LEAD TO TACKLING OUR TISSUE RESPONSE IN INFLAMMATION. SO I HAVE TO THANK ALL THE PEOPLE THAT HAVE DONE THE WORK. THANK YOU VERY MUCH FOR YOUR ATTENTION. >> WHAT CAN YOU TELL US ABOUT THE MESSENGERS OR THE BENEFICIAL EFFECTS TO THE ORGANISMS. >> THE MECHANISM YOU MEAN? >> THE MESSENGER. >> THE RESPONSE? >> OR OTHER BENEFICIAL EFFECTS. >> IN SOME CASES IT'S IN THE CONTEXT THAT'S A STRUCTURAL ELEMENT AND OTHER CASES THEY CAN GO TO THE BONE MARROW AND EFFECT MANY THINGS. MOLECULES TO TACKLE THE IMMUNE SYSTEM WHICH ALLOWS US TO RESPOND. >> WHAT ABOUT THE SHORT CHAIN FATTY ACIDS? >> AND IT CAN HAVE A PROFOUND EFFECT ON THE IMMUNE SYSTEM. >> IS THERE A GENERAL RESPONSE IN OTHER TISSUES AND SKIN? >> I THINK THE LIMITATION IN THE FIELD IS THE NUMBER OF ANTIGENS ARE LOW SO THERE'S NOT MANY TOOLS TO TRACK THEM. WE NEED TO TRACK THE COMPLEXITY OF THE RESPONSES TO UNDERSTAND THE TOOLS. >> ANY OTHER QUESTIONS? >> I THINK IT USED TO BE IN THE G.I. TRACK OR THE NUMBER OF SPECIES? >> SPECIES. >> FOR BACTERIA IT COULD BE AROUND $1,000 PER PERSON BUT 1,000 PER PERSON BUT IT'S PROBABLY NOT WELL DONE OR APPROPRIATE. AT ANY GIVEN TIME IF YOU LOOK AT THE SKIN AND G.I. TRACK IS PROBABLY AN UNDER ESTIMATION. >> AND WHEN I WASH MY HANDS AM I HURTING SOME OF THE MICROBIOME TOO AND WHEN WE DON'T CHANGE THEM THEY'RE EMBEDDED IN STRUCTURES AND THE TREATMENT SO PLEASE WASH YOUR HANDS. >> AND PASSING THE USE OF FECAL TRANSPLANTS WHAT'S THE STATUS? >> THE FIRST LINE HAS BEEN LOOKING AT DIFFERENT COMPANIES AND THE NEXT STEP IS TO CREATE THOSE THAT ARE WELL CONTROLLED AND THE NEXT GENERATION IS TO HAVE A CONTROLLED WAY OF DELIVER THE DIFFERENT DISEASES AND THEY'RE TRYING TO LINK IT TO AUTISM AND OTHER PHENOMENON. THE NEXT GENERATION IS TO LOOK AT WHAT CAN BE GIVEN THAN JUST A TRANSFER. [QUESTION OFF MIC] >> SHE'S MADE IT IN THE REGION THAT IS DIFFERENT AND ONE REGION CAN AFFECT THE BEHAVIOR. I THINK USING THE GENETIC APPROACH CAN HELP IN SOME CASES IN UNDERSTANDING THE MECHANISM THE MICROBE ABLE TO ENGAGE IN SYSTEMS. >> WHEN THE FDA HAS TO TEST A NEW DRUG -- >> IT HAS BEEN SHOWN THE METABOLISM OF DRUG CAN BE AFFECTED BY THE MICROBIOTA AND I THINK IT'S IMPORTANT TO MOVE FORWARD TO STRATIFY BASED ON RESPONDERS OR ON THE LIFE OF A DRUG. I DON'T THINK IT'S PART OF THE CLASSICAL ROUTINE OF CLINICAL TRIAL BUT HOPE IT WILL BE PART OF THE FUTURE. >> NO OTHER QUESTIONS? >> I'M JUST WONDERING IF YOU'VE DONE WORK WITH THE B CELL RESPONSE? >> WE DIDN'T BUT IT'S BEEN DONE BY OTHERS TO LOOK AT THE SURVIVAL OF B CELLS. YES, OTHER PEOPLE HAVE DONE IT. WE DIDN'T. >> OKAY. -- THANK YOU VERY MUCH. >> THANK YOU. IT'S A PLEASURE TO BE HERE AND TALK ABOUT THE MICROBIOME. I HAVE STUDIED TRANSLATION AND IMMUNOLOGY IN HUMANS. AND FROM MICE TO HUMANS AND PRIMATES IS DRIVEN BY THE METAGENOME AND IT'S GENOME IS A COMBINATION OF ALL THE HOST GENES AND IS OUTNUMBERED BY GENES FROM THE MICROBIOME. AND THEY ARE PRESENT IN THE COMPLEX DISEASES WE SEEN BUT IT SHOULD NOT BE SEEN ISOLATE. WHEN WE STUDY MICE, THEY'RE NOT IN A STERILE ENVIRONMENT. WE THINK HUMANS DO BUT THEY LIVE IN A COMPLEX ENVIRONMENT AND HUMANS AND ALL MEMBERS ADOPT THE ENVIRONMENT AND MICE ARE EXPOSED TO STIMULI FROM PATHOGENS, VIRUSES, ALL KINDS OF DISEASES AND ALSO TOXINS AND MOLD THEY'RE EXPOSED TO. WE WOULD ADD THE CONSTANT EXPOSURE GIVE AN ADVANTAGE TO THE HOST AND A MICROBIOME HAS SURVIVAL ADVANTAGES TO THE HOST WHICH WE SHOW AS AN EXAMPLE AS A PROTECTIVE SHIELD. UP CONTRAST WE HAVE THEM ISOLATED UNDER CONTROLLED CONTINUES. AND THEY'VE SEPARATED THEM FROM THE MICROBIOME AND THAT HAS BEEN SELECTED IN THE LABORATORY. SO THE BASIS FOR THIS PRESENTATION WE WOULD ARGUE THERE'S A NATURAL METAORGANISM AND THAT'S WHAT WE GET FROM ANIMAL STUDIES. WE ARGUE A METAORGANISM MAY HAVE LOST THE SHIELD CREATED BY A SYMBIOTIC HOST MICROBIOME INTERACTION AND WE ARRIVED AT THE HYPOTHESIS AND WE KNOW BY HAVING A PERSISTENT VIRUS THAT'S CO-EVOLVED IN THE HOST FOR DECADES LEARNS HOW IT WORKS AND THIS SAY QUESTION WHEN THEY WERE ASKED AND SAID ALL THE QUESTION COMMON SENSE BUT THEY'RE DIFFICULT TO ADDRESS IN A RESEARCH SETTING. SO HE BASICALLY INCORPORATED A UNIQUE APPROACH AND SPEAKS TO THE INTERMURAL RESEARCH PROGRAM AT NIH BECAUSE IT CREATED THE -- INFINITE POSSIBILITIES AND LOOKED AT ANTIBIOTIC TREATED MICE. WHAT COULD WE LEARN IF WE COMPARE THEM TO A NATURAL ENVIRONMENT. AND HOW CAN YOU STUDY THESE? HOW CAN WE FIND THE MICE WE CAN STUDY FOR IN OUR CASE IMMUNE RESPONSES? SO THEY ORIGINATE FROM NORTHERN EUROPE AND JAPAN AND BROUGHT FROM THE EAST COAST MANY CENTURIES AGO AND HAVE THE BASIS FOR THE LAB STRAINS IN THE LABORATORY. HE SAID I'M GOING TO TRACK MICE AND WENT TO THE NATURAL HABITAT OF THE MICE. THEY LIVE IN CLOSE PROXIMITY TO HUMANS. SO HE WENT OUT TO EIGHT LOCATIONS AND HE LOOKED AT THE COLORED DOTS. THESE ARE BASICALLY HORSE BARNS WITHOUT PEST CONTROL SO WE COULD NOT ENCOUNTER RESEARCH FACILITY ESCAPE MICE THERE AND TRACKED MORE THAN 00 MICE. HE TRACKED MORE THAN 800 MICE WHICH WAS CHALLENGING. SO MAKE SURE THEY WERE NOT ESCAPED LABORATORY MICE WE PERFORMED A COMPLEX ANALYSIS. THE OVERARCHING AIM WAS TO FIND THE GENETIC RELATIVE OF A LAB MICE CLOET CLOSELY RELATED. SO THE CLOSEST OF THE STANDARD LABORATORY MICE IN OUR CASE THE STANDARD MICE WE COULD FIND AND WE COLLABORATED WITH GENETICISTS AND THEY HAD A WAY TO ALLOW THE IDENTIFICATION OF MICE AT THE SUBSPECIES LEVEL. YOU'LL SEE HERE THE DIFFERENT MICE HE HAD COLLECTED ALREADY FROM DIFFERENT COUNTRIES IN EUROPE SHOWN IN GREEN AND ASIA AND AS A CONTINENT AND WE SHOW 12 HERE BECAUSE ALL THE DOTS WOULD BE OVERLAPPING. AND THIS IS LOOKING AT THE BOTTOM. AND STANDARD LABORATORY STRAINS AND OTHERS ARE SHOWN IN BLUE. AND IF YOU PERFORM A ANALYSIS WITH COMPLEX STATISTICS YOU SEE THE MARYLAND MICE ARE AMONG THE MICE THAT ARE CLOSEST RELATED TO THE STANDARD LABORATORY STRAIN. THEY COME UP ON TOP IN THE SQUARE AND THE THIRD ARE ON THE RIGHT AND THERE'S NO STATISTICAL SIGNIFICANCE BETWEEN THE TOP FIVE OR SIX OF THE MICE. BUT IT'S NICE TO SEE THE MARYLAND MICE ARE ON TOP SO THEY'RE CLOSELY RELATED TO THE STANDARD LABORATORY ONES. SO THERE'S A MICROBIOME AND IS THERE A DIFFERENCE BETWEEN THE MICE AND THE NEXT SIX STRAINS FROM DIFFERENT VENDORS SHOWN IN BLUE. THE LINES SHOW THE CLUSTER. AND HE SHOWED IN EACH ONE THERE WAS OVERLAP OF THE MICROBIOME. THERE SEEMED TO BE A STABLE MICROBIOME OUT THERE DISTINCT FROM WHAT WE SEE OF THE MICE. AND WE SEE THE DIFFERENCES PRESENTING ONE MOUSE AND YOU SEE THE WHITE ON THE LEFT AND THE LABORATORY SIX MICE ON THE RIGHT AND THERE WERE MANY MORE IN BLUE AS LAB MICE THAN THE WHITE MICE AND THERE WERE MORE BACTERIA IN THE WHITE MICE. AND THERE WAS STATISTICALLY A DIFFERENCE AND AT THE BOTTOM AND THE DIFFERENCE AT THE LEVEL OF ORDER. AND WITH THE MICROBIOTA FROM THE MICE AND THE TISSUE ADD HEERNT A ADHERENT AND SELECTED DONOR MICE AND CAT CATEGORIZED THEM AND ALSO TESTED ALL OF THE DONOR MICE OF THE MICROBIOME FOR COMMON PATHOGENS THAT WOULD NOT BEALLOWED IN OUR FACILITY. YOU SEE THE TESTING OF WHITE MICE FROM LOCATIONS A, B AND C FOR THE COMMON BACTERIA, VIRUSES AND TO OUR SURPRISE WE FOUND QUITE A GREAT PERCENTAGE OF WHITE MICE THAT TESTED FOR ALL THE PATHOGENS BY TESTING AND NOT ALLOWED IN THE FACILITY AND WE LOOKED AT THE MICROBIOTA AND THEY COLONIZED THE MICE AND THEY WERE PREGNANT SO WE TRANSFERRED IN A NATURAL WAY THE MICROBIOTA TO THE OFFSPRING. THIS IS WAS IN THE MICE COLONIZED WITH THE MICROBIOTA LABELLED AS WITE R. SO RECIPIENTS OF THE MICROBIOME AND IT WAS SIMILAR TO WHAT WE HAVE IDENTIFIED IN THE WHITE MICE. AS A TECHNICAL CONTROL WE ALSO TRANSFERRED THE LAB MICE TO THE GERM-FREE MICE TO MAKE SURE THE TRANSFER DIDN'T CHANGE ANYTHING AND THE MICE ARE SHOWN ON THE RIGHT. AND A STUDENT AT MIT IN BOSTON USED ANALYSIS TO BASICALLY IDENTIFIED THE UNIT INDICATED FOR THE LAB FOR THE MICROBIOME AND FOR THE WHITE MOUSE MICROBIOME. HE INDICATED THEY WERE DETECTABLE OVER THE FOUR GENERATIONS OF MICE THAT WE FOLLOWED AND CHARACTERIZED. THE OFFSPRING OF THE MICE THAT RECEIVED THE MICROBIOME WERE NATURALLY COLONIZED AND THEY COMBINED THE BEST SCENARIOS FROM BOTH WORLDS. THEY HAD GENETICS OF THE LABORATORY MICE AND CONTAINING FITNESS-PROMOTING MICROBES FROM THE BIOME AND WE LOOKED AT THEY WOULD HAVE PROTECTED SHIELD WE THINK WAS DEVELOPED BY THE EVOLUTION IN NATURE AND WOULD SHOW A DIFFERENCE RESPONSE TO COMMON DISEASE CHALLENGES THAN THE STANDARD LABORATORY MICE. AND OF NOTE WAS THEY EXCLUDED THE PATHOGENS AND BASICALLY EXCLUDED THE INFLUENCE OF THE DEFLECTION. WE HAD ONLY THE MICROBIOTA. SO WE THEN ASKED THE QUESTION DO THEY PROMOTE HOST FITNESS OF THE GENETICALLY LED MICE AND WE USED A VIRUS AND TOXIN AND ANOTHER MODEL AND WE CHALLENGED THE MICE WITH INFLUENZA VIRUS AND WE SHOWED THE RECIPIENT OF THE WHITE MICE MICROBIOME SURVIVED AN INFECTIOUS DOSE OF INFLUENZA AND RECEIVED THE LAB MOUSE MICROBIOME. THE DIFFERENCE WAS APPARENT QUICKLY SO YOU CAN SEE TWO AND THREE DAYS AFTER INFECTION IT WAS A WHITE MOUSE MICROBIOME AND THE OTHER GROUPS IMMEDIATELY LOSE WEIGHT. AND THIS WAS A BETTER CONTROL OF VIRUS AFTER INFECTION IN THE MICE. SO WHY IS THIS? WE SAW IT IN THE WHITE MICE THAT RECEIVED THE BIOME AND YOU SEE AT THE BOTTOM SLIDE IN THE LUNGS AND THIS WAS ASSOCIATED WITH A DECREASED CYTOKINE PROTEIN IN THE LUNG TISSUE. YOU SEE THE MICE WITH THE WHITE MICE MICROBIOME AND THE CYTOKINES EXCEPT FOR THE IMMUNOEXPRESSIVE CYTOKINE THEY HAD LOWER LEVELS. THE WHITE MOUSE CONFERS THE TRAITS OF THE EXCESSIVE INFLAMMATION AND THERE WERE SOME DEATHS IN HUMANS DUE TO INFLUENZA IS NOT DUE TO THE PATHOG PATHOG PATHOG PATHOGENOSIS OF THE DISEASE AND WE WANTED TO LOOK AT A DIFFERENT MODEL AND THAT'S THE MODEL OF CO COLORECTAL IMUNOGENESIS AND WE HAD AT THE BEGINNING OF THE PERIOD AN INJECTION OF AN AOM. AND FOR THIS TREATMENT YOU SEE IMMEDIATELY A DIFFERENT IN THE INFLAMMATION SCORE AND THE MICE THAT RECEIVED THE WHITE MOUSE MICROBIOME HAD LESS INFLAMMATION THAN THE LAB SIX BIOME. WHEN YOU COUNT THE NUMBER OF TUMORS VISUALIZED BY WHITE DOTS ON THE SLIDE IN THE LEFT YOU SEE THE TUMOR AREA IN THE COLON SIGNIFICANTLY LOWER SCORES FOR THE MICE WITH THE MICROBIOME. AGAIN, IT REDUCED INFLAMMATION IN THE MODEL. AND WE SAW SOMETHING THAT USUALLY IS NOT OBSERVED IN THE MODELS. WE SAW THERE WAS ALSO PROTECTION FROM COLORECTAL CANCER AND YOU CAN LOOK AT THE CARCINOMA AND IT WAS OBSERVED IN THE LAB MICE AND NOT IN THE ANY OF THE MICE WITH THE WHITE MICE MICROBIOME. IF YOU GIVE A BASIS SCORE THE MICE WITH THE MICROBIOME DO MUCH BETTER. SO TO SUMMARIZE THIS, IN THE NATURAL WORLD AND LABORATORY WORLD WE WOULD ARGUE IN THE NATURAL WORLD AS A NATURAL METAORGANISM DRIVEN BY DIVERSE INFLAMMATORY STIMULI AND IN THE LABORATORY WORLD THERE'S A MORE RESTRICTIVE ENVIRONMENT AND A MICROBIOME ORGANISM BUT IT'S NOT EXPOSED TO THE ENVIRONMENTAL CHALLENGES YOU WOULD OTHERWISE SEE IN NATURE. IT CREATED A MODEL WHERE THE GUT MODEL CAN BE TRANSFER TO THE MICE AND IT CREATES THE GENETICS FROM THE MODELS AND THE MICROBIOME OF THE WHITE MICE AND WE SEE INCREASED HOST FITNESS AND LIMITED INFLAMMATION AND TUMOR REGENESIS. WE THINK THIS MODEL WHICH WE ARE NOW USING TO PROTECT THE MECHANISM IN A VAST NUMBER OF DE DISEAS DISEASES WE HOPE MANY MODELS WILL MODEL BETTER COMPLEX DISEASES OR RESPONSES THAT ARE DIFFICULT TO TRANSLATE FROM THE LABORATORY MICE. SO WITH THIS I HAVE ACKNOWLEDGEMENT SLIDES. AS I SAID IN THE PRESENTATION IT WAS DEVELOPED AND EXECUTED BY THE POST DOCTORAL FELLOW IN THE LABORATORY. WE HAD ONE PERSON DRIVING THE RESEARCH AND ANOTHER STUDENT WHO STAYED FOR TWO YEARS AND HELPED AND IS NOW A STUDENT AT BOSTON AND WE HAVE A NEW POST-DOCTORATE FELLOW AND THEY HAVE COLLABORATED FOR THE ANALYSIS AND MICROBIOME ANALYSIS WAS DONE ORIGINALLY BY THE COLLEGE OF MEDICINE AND ANDREW MORGAN AND OTHERS WERE ADDED ON WITH THE UNIQUE GENETICS I SHOWED IN THE SLIDE. THANK YOU FOR YOUR ATTENTION. [QUESTION OFF MIC] >> WE HAVE NOT ANALYZED BUT AT THIS TIME WE HAVE NOT DONE THIS. >> AND -- >> THE QUESTIONS PLEASE GO TO THE MICROPHONE. >> I WAS WONDERING IF YOU'D TRIED THINGS THAT HAVE BEEN TRADITIONALLY HARD TO EFFECT IN THE STANDARD LABORATORY MICE? >> NOT YET. WE'VE BEEN WORKING WITH OTHER COLLABORATORS AND WE HAVE SEEN SOME BENEFITS THERE. >> THANK YOU. IT'S VERY INTERESTING. I HAVE A QUESTION SPECULATIVE ON YOUR HYPOTHESIS. WOULD IT BE BIG TO TAKE FROM RATS TO POPULATIONS IN COUNTRIES THAT DON'T HAVE SO MANY PROTECTED SHIELDS OF ENVIRONMENTS OF GROWING WHEN THEIR HOUSES ARE CONDITIONING -- AIR-CONDITIONING OR ANYTHING BUT THEY'RE EXPOSED TO A NATURAL ENVIRONMENT SO DO YOU THINK HUMAN POPULATIONS IN DEVELOPING COUNTRIES CAN HAVE MICROBIOMES TO CONTEND WITH INFECTIOUS DISEASES? DO YOU THINK YOU CAN EX TRAP LATE THAT HYPOTHESIS? >> A LOT OF STUDY OF NATIVE POPULATIONS AND THE MICROBIOME IS VERY DIFFERENT THAN THE MICROBIOME HERE IN MARYLAND PREVAILS. IF YOU THINK OF THE HYDROGEN HYPOTHESIS HAS A HUGE EFFECT ON ASTHMA AND DIFFERENT DISEASES SO MUCH COVERED IN COUNTRIES AND AS AN EXPOSURE TO MICROBES. >> TO WHAT EXTENT DOES A NEWBORN BABY HAVE THE BUY OME -- BIOME OF AN ADULT? OR DO WE KNOW? >> WE KNOW THE IMMUNE RESPONSE IS TRANSFERRED FROM THE MOTHER'S ANTIBIOTICS AND WE KNOW THE MICROBIOME CHANGES IN EARLY LIFE. I HAVE NOT STUDIED THAT SPECIFICALLY. >> I THINK IT DEPENDS ON IF THE CHILD IS BORN BY CAESAREAN SECTION. THAT'S BECOME A BIG THING. >> SO IF I UNDERSTAND, CORRECT I, YOU'VE BEEN ABLE TO MAINTAIN NATURAL BIOME FROM THE MOUNDS YOU CAN SUSTAIN THAT IN THE LABORATORY, A FORM YOU CAN NOW INTRODUCE MODELS. IS THAT THE DIRECTION YOUR WORK IS TAKING TO SEE WHETHER THERE ARE DIFFERENCES IN THE IMMUNE RESPONSE? >> CORRECT. AND WHAT THE MECHANISMS AND HOW THE BASELINES DIFFER FROM THAT OF LABORATORY MICE. THE STUDIES IN HUMANS I'VE DONE BEFORE HAS INFECTIOUS DOSES OF VIRUSES BECAUSE OF THE HIGH EXPOSURE RATE. AN INFLUENCE TO SEE IMMUNE RESPONSE TO AN ACTUAL INFECTION. THIS SAY RECORD YOU SAID YOU HAD TO INCLUDE. WE KNOW IT'S EVIDENCE FOR HUMANS AS WELL. THE QUESTION WE ALWAYS GET THAT DOESN'T COME UP NOW IS WHETHER HUMANS ARE MORE LIKE MICE. >> WHAT LITERATURE IS FILLED WITH THE STUDIES OF MICROBIOME IN VIRTUALLY EVERY KIND OF DISEASE YOU CAN THINK OF BUT LET'S TALK FOR A MOMENT ABOUT GASTROINTESTINAL AND DELIVER DISEASES. PEOPLE LOOK AT IT AFTER TRANSPLANT. WHAT IS YOUR VIEW AS TO FRARNGLY THE VALUE OF THOSE STUDIES? FRANKLY, THE VALUE OF THOSE STUDIES AND DO THEY ADVANCE OUR KNOWLEDGE OF HOW DISEASE IS INTERACTING WITH THE MICROBIOME OR THE HOST? HOW WOULD YOU GO ABOUT STUDYING THAT PROBLEM? IN THIS, IN YOUR OPINION, NOT THE BEST WAY TO DO IT? >> I THINK WE DON'T KNOW ENOUGH YET. THE HUMAN STUDIES ARE STILL A COLLECTION OF STOOL SAMPLES AND CATEGORIZING THE MICROBIOME IN DIFFERENT STAGES OF DISEASES AFTER DIFFERENT INTERVENTIONS. THIS ALL HAS TO BE SEEN IN THE CONTEXT NOT JUST OF THE DISEASE BUT ALSO OF THE ENTIRE HISTORY OF A PATIENT. AND IT'S VERY DIFFICULT TO INTERPRET. IT'S NOT JUST US ASKING WHO IS THERE IN TERMS OF MICROBIOME BUT A FUNCTION OF THE MICROBIOME AND MAYBE THEIR DIFFERENT COMMUNITIES OF MICROBYE MICROBIOTA AND THERE STILL NEED TO BE CATALOGING. >> I HAVE A QUESTION OF THE MICROBIOME IN THE LAB MOUSE. THE DIET IS DIFFERENT IN THE NATURAL MOUSE THAN THE LAB MOUSE AND WHAT BEHAVIOR CHANGES DID YOU SEE? >> WITH THE DIET WE WERE SURPRISED. ALL THE CHANGES IN SOCIAL STRUCTURE AND THE LIVING ENVIRONMENT, DAY/NIGHT CYCLE, TEMPERATURE AND MOST OF ALL, DIET, DID NOT AFFECT THE MAINTENANCE OF THE MICROBIOME IN THE COLONIES WE KEPT FOR FOUR TO SEVEN GENERATIONS. WE DIDN'T GIVE THEM THE NATURAL DIET BUT THE LAB DIET. WE THINK NOW THE MICROBIOME IS VERY STABLE. WE ALSO KNOW FROM STUDIES THAT ARE PUBLISHED ON WHITE MICE THAT ARE TRAPPED IN DIFFERENT SEASONS THAT THE CHANGES INDICT -- IN DIET THERE'S DIFFERENT CHANGES IN THE MICROBIOME AND IT COMES BACK TO THE SAYING IT WAS A YEAR BEFORE IN THE SAME SEASON. I CAN'T ANSWER YET. I HOPE IN THE NEXT DEMYSTIFYING MEDICINE. >> WHAT DO YOU THINK WOULD WHAT HAVE HAPPENED IF YOU HAD GIVEN THE MICE STABLE MICROBIOTA ANTIBIOTICS AND A BARE BONES LABORATORY DIET. DO YOU THINK THAT WOULD HAVE CHANGED? >> WE DON'T KNOW. THAT'S ONE THING THAT COULD BE TESTED TO SEE IF IT COMES BACK TO WHERE IT WAS. MAYBE IT'S LESS WELL ADOPTED TO OTHER CHALLENGES THAT ARE NOT THAT NATURE. >> WHEN WE STARTED, MAYBE WE SHOULD END WAY QUESTION WITH THE CREATOR. WHEN PEOPLE GO TO THE SUPER MARKET AND BUY SOMETHING CALLED PROBIOTIC HOW LIVE ARE THOSE ORGANISMS. DO THEY DO ANY GOOD? MY UNDERSTANDING IS THEY'RE NOT REGULATED BY THE FDA BUT THE DEPARTMENT OF AGRICULTURE AS A FOOD SUPPLEMENT. DO WE HONESTLY KNOW ANYTHING WITH THE PROBIOTIC -- >> I'D BE HESITANT IN ANSWERING THE QUESTION BUT I KNOW FROM HEPATOLOGY PRACTICE ANY TYPE OF SUPPLEMENT THAT IS NOT REGULATED BY FDA YOU CAN JUST TAKE OVER THE COUNTER THAT'S SUPPOSED TO BE GOOD FOR YOUR HEALTH CAN HAVE DETRIMENTAL AFFECTS ON ANYTHING. >> I THOUGHT IF YOU WANT TO FOLLOW ON THE LACTO BACILLUS YOU SHOULDN'T GIVE IT BY MOUTH BUT BY RECTUM WHICH STANDS A BETTER CHANCE OF DOING SOMETHING. WE WANT TO THANK YOU VERY MUCH, BARBARA. >> THAT WAS GREAT. >> THAT WAS EXCELLENT.