>> WELCOME TO DAY 1.
I'M ASHLEY VARGAS AT THE EUNICE
KENNEDY SHRIVER CENTER.
IT'S MY GREAT PLEASURE TO
WELCOME YOU TO THE OPENING OF
OUR TWO-DAY JOINT NIH AND FDA
WORKSHOP, EXPLORING THE SCIENCE
SURROUNDING THE SAFE USE OF
BIOACTIVE INGREDIENTS IN INFANT
FORMULA, CONSIDERATIONS FOR AN
ASSESSMENT FRAMEWORK.
WORKSHOP IS NOT INTENDED TO BE
ADVISORY TO ANY FEDERAL AGENCY,
THE FOCUS OF THIS WORKSHOP IS
THE STATE OF THE SCIENCE,
PROMISING ADVANCES, RESEARCH
OPPORTUNITIES IN THIS SPACE.
TO DIVE DEEPER INTO THE PURPOSE
OF THIS WORKSHOP IT IS TO
EXPLORE THE SCIENCE OF BIOACTIVE
HUMAN MILK COMPONENTS AND
ANALOGS THAT COULD BE INCLUDED
AS INGREDIENTS IN INFANT
FORMULA.
AS CAN IMAGINE, THIS COULD BE A
LONG CONVERSATION, SO SINCE WE
HAVE TWO DAYS TO TALK ABOUT THIS
WE'VE SET GUARD RAILS.
WE'RE FOCUSED ON INFANT FORMULA
INTENDED FOR USE IN TERM AND
HEALTHY INFANTS UP TO 12 MONTHS
OF AGE, AND YOU MIGHT FIND
EXAMPLES THROUGHOUT THE
PRESENTATIONS ON PRE-TERM
INFANTS OR HUMAN MILK ITSELF OR
INFANTS WITH CONDITIONS, BUT
REALLY THE FOCUS DURING THE NEXT
TWO DAYS IS HEALTHY TERM
INFANTS.
WE'VE ALSO PUT TOGETHER A
DEFINITION OF BIOACTIVE
INGREDIENTS FOR THE SAKE OF THIS
WORKSHOP, SO I WON'T READ THE
WHOLE THING TO YOU BUT THE GIST
IS BIOACTIVE INGREDIENTS ARE
SYNTHETIC OR NON-HUMAN MILK
DERIVED INGREDIENTS MIMICKING
COMPONENTS TYPICALLY PRESENT IN
HUMAN MILK, NOT TRADITIONAL
CONSIDERED ESSENTIAL NUTRIENTS.
DURING THIS WORKSHOP, WE'RE
TRULY HONORED TO HAVE IN THE
VIRTUAL ROOM WITH US WORLD
RENOWNED SCIENTISTS IN EARLY
LIFE.
SO IN THE PRE-WORKSHOP MATERIALS
THERE IS AN OVERVIEW OF NIH'S
INTEREST IN THIS FIELD AND ALSO
THE FDA REGULATORY FRAMEWORK IN
THIS SPACE.
HOWEVER, SINCE WE HAVE SUCH
FANTASTIC SCIENTISTS IN THE ROOM
WITH US TODAY, WE'RE GOING TO
FOCUS ON THE SCIENCE,
SPECIFICALLY THE STATE OF THE
SCIENCE ON THE SAFETY AND
FUNCTION OF INFANT FORMULA
BIOACTIVE INGREDIENTS.
TO THAT END WE'VE PUT TOGETHER
FIVE SCIENTIFIC SESSIONS FOR YOU
OVER TWO DAYS, SO THE FIRST
SESSION IS GOING TO FOCUS ON
HOW, WHERE, EVEN WHEN INFANT
FORMULA AND ITS INGREDIENTS CAN
PLAY A ROLE IN INFANT
DEVELOPMENT, SESSION 2 WILL
FOCUS ON HOW HUMAN MILK IS USED
AS A REFERENCE FOR INFANT
FORMULA AND SOME CHALLENGES
ABOUT A DIVERSE REFERENCE.
SESSION 3 IS GOING TO MOVE INTO
A LITTLE BIT MORE OF A
TECHNICAL REALM, AFFECTING
FUNCTION AND SAFETY.
SECTION 4, AND SESSION 5
BIOACTIVE INGREDIENTS AND
FUNCTION AND SAFETY.
WE GAVE SPEAKERS VERY
CHALLENGING QUESTIONS AND BIG
TOPICS TO COVER IN A SHORT
AMOUNT OF TIME, WE ALSO ASKED
THEM TO THINK ABOUT FOR EACH OF
THESE QUESTIONS HOW COULD WE
MEASURE THIS TO DETERMINE
FUNCTION OR SAFETY?
I'M NOT GOING OVER THE DETAILED
AGENDA.
THIS IS AVAILABLE ON THE
WORKSHOP WEBSITE.
BUT WE HAVE SEVERAL BREAKS BUILT
IN THROUGHOUT THE DAY, WE'LL BE
FLEXIBLE WHEN THOSE OCCUR BUT
RIGHT NOW THE FIRST ONE IS
SCHEDULED FOR A LUNCH BREAK IN
EASTERN TIME.
AND TOMORROW WE HAVE TIME FOR
SPEAKER Q&A AND DISCUSSION.
WE'RE EXCITED ABOUT THIS AS THE
FEDERAL TEAM TO DIVE INTO THESE
BIG OVERARCHING QUESTIONS TO GET
A FEEL FOR WHERE THE STATE OF
THE SCIENCE IS AND PICK THE
BRAINS OF THE FABULOUS SPEAKERS
AVAILABLE TO US TODAY AND
TOMORROW.
SO WE'RE LOOKING FORWARD TO THIS
TODAY AND TOMORROW AS WE GO
THROUGH THE DISCUSSION PERIODS.
AS I SAID, DAY 2 WILL START WITH
SESSION 4, WE'LL HAVE BREAKS
AGAIN BUILT IN, A MUCH LONGER
SPEAKER DISCUSSION SECTION.
SO WE, AGAIN, AS FEDERAL STAFF
ARE VERY EXCITED ABOUT THE
DISCUSSION PIECE IN ADDITION TO
THE WONDERFUL PRESENTATIONS
WE'LL HEAR IN THE NEXT TWO DAYS.
I WANT TO THANK NICHD FOR THE
FUNDING FOR THIS WORKSHOP AND
TECHNICAL SUPPORT FROM LIZ,
LIZA, SEBASTIAN, PAT, AND ALEX
WHO WE HAVE WITH US AND I THANK
THE PLANNING COMMITTEE, MANY OF
WHOM YOU'LL MEET TODAY OR
TOMORROW AS THEY SERVE IN THE
ROLE OF MODERATOR.
THIS IS JOINT NIH AND FDA
PLANNING COMMITTEE, WORKING
TOGETHER FOR OVER A YEAR TO PUT
TOGETHER A PROGRAM THAT REALLY
MEETS THE SHARED PURPOSE OF OUR
INSTITUTES, OF THE SCIENCE-BASED
INSTITUTIONS AND SHARED VISION
OF HEALTHY AND SAFE LIVES FOR
ALL CHILDREN.
WE HOPE THIS IS A FIRST OF MANY
WORKSHOPS BUILDING ON THE
PARTNERSHIP BETWEEN THE TWO
VITAL PUBLIC HEALTH AGENCIES.
THIS IS JUST A CALL-OUT AND
REMINDER THERE ARE MANY
IMPORTANT LINKS INCLUDING THAT
PRE-SESSION THAT GOES OVER THE
BACKGROUND INFORMATION FROM BOTH
NIH AND FDA THAT YOU CAN PERUSE
AT YOUR LEISURE.
ALSO THE AGENDA IS THERE, THE
LINKS TO WATCHING THE
PRESENTATIONS LIVE, AND, AGAIN,
WE'LL BE MONITORING THIS E-MAIL
ADDRESS THROUGHOUT THE
PRESENTATIONS SO PLEASE FEEL
FREE TO SUBMIT YOUR QUESTIONS
AND COMMENTS AS WE PROCEED
THROUGH THE WORKSHOP.
I HAVE THE GREAT PLEASURE OF
INTRODUCING DR. DIANA BIANCHI,
DIRECTOR OF EUNICE KENNEDY
SHRIVER INSTITUTE OF CHILD
HEALTH AND HUMAN DEVELOPMENT WHO
WILL GIVE REMARKS ON BEHALF
NICHD, AND FOLLOWING DR. SUSAN
MAYNE FROM FDA.
>> THANK YOU FOR THE OPENING
REMARKS.
I WOULD LIKE TO ADD MY WELCOME
TO EVERYONE FOR THIS IMPORTANT
TWO-DAY WORKSHOP, THE NIH IS
CO-HOSTING WITH OUR SISTER
AGENCY, THE FDA.
AS YOU KNOW, MOTHER NATURE HAS
HISTORICALLY DESIGNED HUMAN MILK
AS A CHILD'S FIRST FOOD, AND
THIS HAS EVOLVED OVER THOUSANDS
OF YEARS TO BECOME THE EXEMPLAR
OF PRECISION NUTRITION.
WE KNOW HUMAN MILK IS A SOURCE
OF LIFE-SUSTAINING NUTRIENTS,
AND OTHER BIOACTIVE COMPONENTS,
THAT ARE THE RESULT OF A COMPLEX
ECOLOGY TO MEET THE NEEDS OF A
SPECIFIC INFANT.
INDEED THE U.S. GOVERNMENT AND
MANY PROFESSIONAL SOCIETIES
RECOMMEND THAT HUMAN MILK BE THE
SOLE SOURCE OF NUTRITION FOR
INFANTS UP TO AGE SIX MONTHS.
THAT SAID, ALTHOUGH
APPROXIMATELY 80% OF INFANTS IN
THE UNITED STATES WILL RECEIVE
SOME HUMAN MILK, ONLY ABOUT 25%
ARE EXCLUSIVELY FED HUMAN MILK
UNTIL THE RECOMMENDED SIX MONTHS
OF AGE.
THEREFORE WE RECOMMEND THAT ALL
INFANTS REGARDLESS OF THEIR
ACCESS TO HUMAN MILK DESERVE
ACCESS TO A SAFE AND EFFECTIVE
SOURCE OF NUTRITION.
WE NEED A KNOWLEDGE BASE TO
SUPPORT CREATION OF RELEVANT
EVIDENCE-INFORMED STANDARDS OF
NUTRITION CARE FOR INFANTS.
AGENCIES CHARGED WITH
ADJUDICATING SAFETY OF
SUBSTANCES ADDED TO MILK
SUBSTITUTION SUCH AS INFANT
FORMULA NEED APPROPRIATE
RESOURCES UPON WHICH TO BASE
THEIR DELIBERATIONS.
FINALLY, A NEED EXISTS TO
SUPPORT DECISIONS REGARDING SAFE
AND EFFICACIOUS PRACTICES
EMPLOYED CURRENTLY BY MOTHERS
AND OTHER CAREGIVERS.
TO STIMULATE DISCUSSION, AND
IDENTIFY RESEARCH OPPORTUNITIES
TO FILL GAPS, IN SCIENTIFIC
KNOWLEDGE, OVER THE NEXT TWO
DAYS WE WILL HEAR FROM EXPERTS
IN THE FIELD OF INFANT
NUTRITION, AND THEY WILL ADDRESS
FIVE MAJOR TOPICS.
NUMBER ONE, NORMAL INFANT
DEVELOPMENTAL OUTCOMES.
NUMBER TWO, THE USE OF HALLELUIA
MILK AS A REFERENCE FOR
BIOACTIVE INGREDIENTS IN INFANT
FORMULA.
NUMBER THREE, POTENTIAL IMPACT
OF BIOACTIVE INGREDIENT
PROCESSING ON THE SAFETY AND
FUNCTION OF INFANT FORMULA.
NUMBER FOUR, WHETHER BIOACTIVE
INGREDIENTS FROM DIFFERENT
SOURCES ARE FUNCTIONALLY
EQUIVALENT.
NUMBER FIVE, CONSIDERATIONS
REGARDING THE INTERACTIONS
BETWEEN BIOACTIVE INGREDIENTS
AND OTHER COMPONENTS THAN
FORMULA.
NOT ONLY IS THIS WORKSHOP A
REFLECTION AND DEMONSTRATION OF
THE COLLABORATIVE NATURE OF THE
RELATIONSHIP BETWEEN THE NIH AND
FDA, BUT IT'S ALSO A PRODUCT OF
THE FDA/NIH JOINT AGENCY ON
NUTRITION, ALSO KNOWN AS THE JAN
WORKING GROUP, FORMED IN 2016 TO
FACILITATE HIGH QUALITY
NUTRITION RESEARCH TO IMPROVE
PUBLIC HEALTH OUTCOMES ACROSS
THE LIFESPAN, NUMBER ONE,
REDUCING RISK FACTORS FOR AND
INCIDENCE OF NUTRITION-RELATED
CHRONIC DISEASE, AND NUMBER TWO,
TO INFORM NUTRITION-RELATED
REGULATORY DECISIONMAKING AND
CONSUMER OUTREACH AND EDUCATION
RELATED TO NUTRITION.
A STRATEGIC GOAL OF THE JOINT
AGENCY IS TO RESEARCH RESEARCH
GAPS RELATED TO EARLY LIFE AND
NUTRITION DURING PREGNANCY
PARTICULARLY FEEDING PRACTICES
AND HUMAN MILK COMPOSITION, TO
INFORM REGULATORY DECISION
MAKING.
OUR HOPE IS THAT THIS TWO-DAY
WORKSHOP WILL ACCOMPLISH THIS
GOAL.
THIS WORKSHOP, OUR COMMITMENT TO
JAN AND RELATED EFFORTS LIKE THE
BEGIN PROJECT AND CURRENT
FUNDING OPPORTUNITIES IN EARLY
LIFE NUTRITION FROM THE NIH ARE
DEMONSTRATION OF OUR
INSTITUTIONAL COMMITMENT TO
NUTRITION RESEARCH EVIDENCED BY
NUTRITION BEING A CROSS-CUTTING
THEME THROUGHOUT THE 2020 NICHD
STRATEGIC PLAN.
WE RECOGNIZE NUTRITION'S
UBIQUITOUS IMPORTANCE ACROSS THE
LIFESPAN ALIGNED WITH THE NIH
RESEARCH STRATEGIC PLAN.
FURTHER, THE NICHD STRATEGIC
PLAN BOLDLY PUTS FORTH THE GOAL
FOR INSTITUTE OPTIMIZING INFANT
SURVIVAL SYNTHESIZING HUMAN
MILK.
I'D LIKE TO THANK THE NIH AND
FDA STAFF MEMBERS FOR ORGANIZING
THIS WORKSHOP, IT'S BEEN OVER A
YEAR IN PLANNING AS YOU HEARD.
I LOOK FORWARD TO THE ENSUING
DISCUSSIONS.
AND NOW I WOULD LIKE TO TURN THE
FLOOR OVER TO MY COLLEAGUE FROM
FDA.
DR. SUSAN MAYNE.
>> GOOD MORNING, EVERYONE.
I WANT TO THANK MY GOOD FRIEND
AND COLLEAGUE DR. BIANCHI, AND I
WOULD LIKE TO ADD A WARM WELCOME
TO EVERYONE WHO IS JOINING
TODAY.
I UNDERSTAND WE HAVE A LARGE
NUMBER AND WIDE RANGE OF FOLKS
PARTICIPATING FROM INDUSTRY,
ACADEMIA, FROM FEDERAL, STATE
AND LOCAL GOVERNMENTS AND MANY
MORE.
YOU MAY OR MAY NOT KNOW OUR
CENTER REGULATES SAFETY AND
LABELING OF 80% OF THE FOOD
SUPPLY WHICH INCLUDES REGULATORY
AUTHORITY OVER INFANT FORMULA.
WE WORK WITH COLLEAGUES ACROSS
THE FEDERAL GOVERNMENT AND WE
HAVE AN ESPECIALLY CLOSE WORKING
RELATIONSHIP WITH OUR NIH
COLLEAGUES.
ROBUST SCIENCE IS THE FOUNDATION
AND BASIS FOR REGULATORY
DECISION MAKING.
EARLIER IN MY CAREER BEFORE I
CAME TO THE FDA, I WAS A
PROFESSOR AT YALE AND I WAS
PRINCIPAL INVESTIGATOR ON
NUMEROUS RESEARCH GRANTS FUNDED
BY THE NIH FOR MANY YEARS.
I WAS ALSO A MEMBER OF THE BOARD
OF SCIENTIFIC COUNSELORS AT ONE
OF THE NIH INSTITUTES.
SO I'VE HAD A LOT OF EXPERIENCE
IN WORKING WITH THE NIH AND OF
IN MANY DIFFERENT CAPACITIES.
I TRULY UNDERSTAND JUST HOW
IMPORTANT THE WORK OF THE NIH IS
AND HOW CRITICAL THE
RELATIONSHIP IS BETWEEN OUR TWO
AGENCIES.
FROM OUR PERSPECTIVE, WE BELIEVE
THERE CONTINUES TO BE A STRONG
DEMAND FOR NUTRITION RESEARCH TO
HELP INFORM IMPORTANT SCIENTIFIC
GAPS IN OUR UNDERSTANDING, MANY
OF WHICH HAVE IMPLICATIONS FOR
REGULATORY WORK AT THE FDA.
WE PARTNER WITH NIH IN
IDENTIFYING RESEARCH GAPS THAT
ARE ESPECIALLY IMPORTANT FOR OUR
WORK, SUCH AS INFANT AND
PEDIATRIC NUTRITION.
WE'LL WELL POSITIONED TO PROMOTE
HEALTHY DIETARY PATTERNS AND
CONSUMPTION OF ESSENTIAL
NUTRIENTS IN YOUNG CHILDREN AND
TO PROTECT THE NUTRITION AND
HEALTH OF THE MOST VULNERABLE
AMONG US.
THIS IS ESPECIALLY IMPORTANT
GIVEN THAT THE MOST RECENT
ADDITION OF THE DIETARY
GUIDELINES FOR AMERICANS FOR THE
FIRST TIME INCLUDED DIETARY
GUIDANCE FOR CHILDREN UNDER 2
YEARS OF AGE, AS MOST OF YOU
ARE AWARE.
THIS IS A CRITICALLY IMPORTANT
PERIOD IN GROWTH AND
DEVELOPMENT, AND WHILE WE NOW
HAVE DIETARY GUIDANCE, RESEARCH
GAPS REMAIN.
IT IS THE RECOMMENDED AND
PREFERRED SOURCE OF NUTRITION
FOR INFANTS, FORMULA IS A MAJOR
AND SOMETIMES SOLE SOURCE OF
NUTRITION FOR INFANTS WHO CANNOT
BE EXCLUSIVELY BREASTFED.
APPROXIMATELY 75% OF INFANTS IN
THE U.S. RECEIVE SOME INFANT
FORMULA OR OTHER NON-BREAST MILK
NUTRITION BY SIX MONTHS OF AGE.
ALL INFANT FORMULA MARKETED IN
THIS COUNTRY MUST MEET FEDERAL
NUTRIENT REQUIREMENTS AND
FORMULA MANUFACTURERS MUST
NOTIFY THE FDA PRIOR TO
MARKETING A NEW FORMULA.
WE KNOW MANUFACTURERS ARE VERY
INTERESTED IN INCLUDING A
VARIETY OF NEW INGREDIENTS IN
INFANT FORMULA, AND FDA IS
RESPONSIBLE FOR EVALUATING THE
SAFETY OF THESE INGREDIENTS,
SPECIFICALLY FOR THIS INFANT
POPULATION.
HOWEVER FOOD TECHNOLOGY AND
INNOVATION ADVANCE, THERE WILL
BE UNANSWERED QUESTIONS THAT
NEED TO BE ADDRESSED BY
RESEARCH.
AND SO I AM PARTICULARLY GLAD
FDA IS COLLABORATING WITH NIH ON
THIS INITIATIVE, AND TO BE
JOINTLY HOSTING THIS TWO-DAY
WORKSHOP ON EXPLORING THE
SCIENCE SURROUNDING THE SAFE USE
OF BIOACTIVE INGREDIENTS IN
INFANT FORMULA, AND FOCUSING ON
THE STATE OF THE SCIENCE OF THE
FUNCTIONAL ASPECTS OF
BIOLOGICALLY ACTIVE HUMAN MILK
COMPONENTS AND ANALOGS,
IMPLICATIONS FOR SAFETY
ASSESSMENT WHEN USED IN INFANT
FORMULA.
I WANT TO ECHO DR. BIANCHI'S
THANKS TO STAFF, YOU'VE HEARD
STAFF HAS BEEN WORKING TOGETHER
FOR THE LAST YEAR.
ALSO THANKS TO ALL THE SPEAKERS
AND ALL THE PARTICIPANTS WHO ARE
JOINING US HERE TODAY FOR THIS
VERY IMPORTANT WORKSHOP.
IT PROMISES TO BE AN EXCITING
AND ILLUMINATING TWO DAYS, BUT
WE REALLY BELIEVE IT WILL HELP
ADVANCE THE SCIENCE ON THIS
CRITICALLY IMPORTANT TOPIC.
THANK YOU.
I'LL TURN IT BACK OVER TO ASHLEY
AT THIS POINT TO CONTINUE THE
PROGRAM.
>> I'M NOT ASHLEY, I'M DREW.
THANK YOU FOR THE OPENING
REMARKS.
I WANT TO ECHO EVERYTHING SAID
AND CALL OUT ASHLEY AND ALL THE
WORK SHE'S DONE WITH EVERYONE TO
PUT THIS TOGETHER.
I HAVE THE PRIVILEGE OF KICKING
OFF THE MEETING.
SO, WELCOME TO SCIENTIFIC
SESSION NUMBER 1.
NORMAL INFANT DEVELOPMENTAL
OUTCOMES.
I'M DREW BREMER, FROM NICHD.
I HAVE THE HONOR OF
CO-MODERATING THIS SESSION WITH
MY COLLEAGUE DR. APRIL
NEAL-KLUEVER.
THE GOAL OF THIS FIRST SESSION
AS ASHLEY MENTIONED IS REALLY TO
SET THE STAGE FOR THE WORKSHOP
AND SESSIONS TO COME BY
ADDRESSING HOW, WHERE, AND WHEN
INFANT FORMULA AND BIOACTIVE
INGREDIENTS PLAY A ROLE IN
INFANT DEVELOPMENT.
I'M GIVE A BRIEF INTRODUCTION OF
SPEAKERS IN PRESENTATION ORDER.
FULL BIOGRAPHIES CAN BE FOUND AT
THE WORKSHOP WEBSITE.
QUESTIONS AND COMMENTS CAN BE
SUBMITTED TO THE E-MAIL ADDRESS
IN REAL TIME THROUGHOUT THE
SESSION.
WE'LL MODERATE A BRIEF
QUESTION-AND-ANSWER SESSION
AFTER EACH PRESENTATION
DEPENDING ON THE TIME.
FIRST IS DR. JOSEPH NIU,
UNIVERSITY OF FLORIDA, A
PROFESSOR OF PEDIATRICS AND
INTERNATIONALLY RECOGNIZED FOR
GASTROENTEROLOGY AND NUTRITION,
FOCUSING ON INTESTINAL
MICROBIOME, METABOLOME, MUCOSAL
IMMUNOLOGY, THIS MORNING WILL
SPEAK ON NORMAL INFANT
DEVELOPMENTAL OUTCOMES AS THEY
RELATE TO THE GASTROINTESTINAL
SYSTEM.
SECOND IS DR. MEGAN AZAD,
ASSOCIATE PROFESSOR OF PEDIATRIC
AND CHILD HEALTH, UNIVERSITY OF
MANITOBA, TIER 2 CANADA RESEARCH
CHAIR IN DEVELOPMENTAL ORIGINS
OF CHRONIC DISEASE.
HER RESEARCH PROGRAM IS FIRST OF
FOCUSED ON INFANT NUTRITION AND
MICROBIOME, DEVELOPMENT,
RESILIENCE.
THIRD IS DR. KIRSI JARVINEN-SEPP
ORGANIZATION, UNIVERSITY OF
ROCHESTER, ASSOCIATE PROFESSOR
OF PEDIATRICS, MEDICINE,
MICROBIOLOGY, IMMUNOLOGY,
DIRECTOR OF THE CENTER FOR FOOD
ALLERGY AT THE UNIVERSITY OF
ROCHESTER IN NEW YORK.
HER INTEREST LIES IN ALL ASPECTS
OF FOOD ALLERGY AND SHE WILL
SPEAK ON NORMAL INFANT
DEVELOPMENTAL OUTCOMES RELATES
TO THE IMMUNE SYSTEM.
AND LAST FOURTH SPEAKER DR.
MANDY BROWN BELFORT FROM
HARVARD, NEONATOLOGIST,
ASSOCIATE PROFESSOR OF
PEDIATRICS AT HARVARD MEDICAL
SCHOOL, FOCUSING ON INFLUENCE OF
EARLY LIFE NUTRITIONAL EXPOSURES
ON OUTCOMES LATER IN LIFE AND
SHE WILL SPEAK ON NORMAL INFANT
DEVELOPMENTAL OUTCOMES RELATING
TO NEUROLOGICAL SYSTEM.
WE WILL DO A SHORT QUESTION AND
ANSWER AFTER EACH.
I TURN THE FLOOR OVER TO YOU,
THANK YOU, ANDREW, FOR THE VERY
NICE INTRODUCTION.
I'D LIKE TO THANK THE ORGANIZERS
OF THIS WORKSHOP FOR INVITING ME
TO DO THIS INTRODUCTORY TALK,
I'M GOING TO TALK ABOUT THE
DEVELOPING GASTROINTESTINAL
TRACT, NUTRITION AND
IMPLICATIONS FOR FORMULA, ALL IN
15 MINUTES, BELIEVE IT OR NOT.
NO RELATIVE CONFLICTS, I'LL TALK
ABOUT INTESTINAL GROWTH,
CONSIDERATION FOR BIOACTIVE
INGREDIENTS AND THEN SOME OF THE
FUNCTIONAL ASPECTS OF THE
GASTROINTESTINAL DEVELOPMENT
INCLUDING DIGESTION, ABSORPTION,
ASSIMILATION OF MACRONUTRIENTS,
INTERACTIONS OF THE ENVIRONMENT
AND INTRINSIC DEVELOPMENTAL
TRAJECTORIES AND SOME CLINICAL
DILEMMAS WE FACE.
LET'S TALK ABOUT THE PAST,
PRESENT AND FUTURE.
ON THE LEFT WE SEE THE PAST AND
PRESENT.
SO IN TERMS OF OVERALL
NUTRITION, ONE OF THE AREAS THAT
HAS BEEN VERY IMPORTANT IS
SOMETHING CALLED THE FOOD
PYRAMID, NOW BEING DISPLACED BY
MANY DIFFERENT KINDS OF
PARADIGMS INCLUDING A MY PLATE,
PRIMARILY FOR ADULTS.
IN BABIES WE HAVE A GROWTH
CURVE.
WE FOLLOW GROWTH CURVES VERY
CAREFULLY, BOTH IN NEONATOLOGY
AS WELL AS PEDIATRICS.
BUT ONE OF THE PROBLEMS WITH
THESE GROWTH CURVE, THEY ARE
BASED ON GAUSSIAN STATISTICS,
AND THERE'S SOME PROBLEMS WITH
GAUSSIAN STATISTICS.
I THINK WE'RE BEGINNING TO FIND
THAT ONE OF THE PROBLEMS THAT WE
HAVE WITH GROWTH CURVES IS ONCE
WE START SEEING A BABY FALLING
OFF THE GROWTH CURVES, IT'S
ALREADY TOO LATE.
AND WE NEED TO HAVE SOME WAYS
THAT WE MIGHT BE ABLE TO PREDICT
WHICH BABIES WILL BE THE MOST
LIKELY TO FALL OFF GROWTH CURVES
AND I THINK WE'RE DEVELOPING
SOME TECHNOLOGIES TO BE ABLE TO
DO THAT.
I'LL TOUCH ON THESE AS WE MOVE
FORWARD HERE.
AND WE ALSO HAVE THIS IDEAL OF
HUMAN MILK AS A CONDITIONALLY
PERFECT MODEL.
WHAT KIND OF HUMAN MILK?
ARE WE TALKING ABOUT COLOSTRUM,
TRANSITIONAL MILK?
WHERE WITH REGOING IN THE
FUTURE?
WE'RE GOING TO BE TALKING ABOUT
THE TRIAD OF NUTRIENTS, WE NO
LONGER THINK OF THE MOTHER AND
BABY AS A DIET BUT MICROBIAL
ECOSYSTEM.
WE'LL TALK -- IN THE FUTURE
WE'RE GETTING INTO DYNAMIC
RATHER THAN POPULATION-BASED
PARADIGMS.
WE'LL GET INTO MULTI-OMICS,
ARTIFICIAL INTELLIGENCE.
AND NOT ONLY WILL WE BE TALKING
ABOUT HUMAN MILK COMPOSITION AS
A STATIC PHENOMENA BUT ALSO
DYNAMIC PHENOMENA, VERY
IMPORTANT AS A MODEL.
HERE WE HAVE MULTI-OMICS, MIXED
WITH ARTIFICIAL INTELLIGENCE FOR
THE FUTURE.
THIS IS A PAPER I'M SURE MANY OF
YOU ARE FAMILIAR WITH AND WE
HAVE SEVERAL OF THE AUTHORS ON
THIS CALL TODAY.
AND THIS IS A PUBLICATION THAT
CAME OUT FAIRLY RECENTLY, THE
NEED TO STUDY HUMAN MILK AS
BIOLOGICAL SYSTEM.
I HAVE SOME OF THE IMPORTANT
PARTS OF THIS UNDERLINED HERE.
HUMAN MILK COMPOSITION AND
RESULTING FUNCTION IS MORE THAN
THE SUM OF ITS PARTS.
WE HAVE TO THINK ABOUT BREAST
MILK NOT ONLY AS -- AND
BREASTFEEDING AS HELPING THE
INFANT BUT PERHAPS ALSO HELPING
THE MOTHER.
SO WE ALSO HAVE TO THINK ABOUT
BREAST MILK AS NOT JUST FOOD FOR
INFANTS BUT COMPONENTS AND
MATERNAL-INFANT INTERACTIONS ARE
EXTREMELY IMPORTANT.
AND THESE ARE GOING TO BE VERY
TOUGH TO BE ABLE TO MIMIC WITH
FORMULAS.
SO LET'S TALK ABOUT THE
INTESTINE.
IT'S VERY VERSATILE.
IT'S NOT ONLY A DIGESTIVE
ABSORTIVE, IT'S THE LARGEST
IMMUNE ORGAN THE BODY.
IT'S THE ORIGIN OF A HUGE
PERCENTAGE OF METABOLITES.
IT HARBORS ENTERIC NERVOUS
SYSTEM, INTEGRAL FOR GUT-BRAIN
ACCESS AND LAST FOUR POINTS WILL
BE DISCUSSED MORE IN THE NEXT
COUPLE LECTURES BY MEGAN, KIRSI
AND MANDY.
WHAT ABOUT GROWTH OF INTESTINE?
THERE'S A HUGE GROWTH IN FETAL
LIFE IN THE INTESTINE.
THIS CONTINUES MAYBE NOT TO THE
SAME EXPONENTIAL DEGREE AS IN
THE FETUS BUT AFTER BIRTH WE
HAVE A CONTINUED AMOUNT OF
GROWTH.
AT BIRTH INTESTINAL LENGTH OF
THE SMALL IS 200 CENTIMETERS,
COLON 75 CENTIMETERS.
THIS APPROXIMATELY DOUBLES IN
THE FIRST YEAR AFTER BIRTH.
AND WITH THE SURFACE, WE HAVE IN
THE ADULT A SURFACE AREA THAT
APPROXIMATES THE SIZE OF A
TENNIS COURT, A HUGE AMOUNT OF
DEVELOPMENT THAT OCCURS.
HERE IS A PICTURE OF A VERY
FAMOUS NUTRITIONIST, DR. ELSIE
WIDDOWSON.
THE SUCKLED PIG'S DUODENUM GAINS
42% OF WEIGHT IN THE FIRST 24
HOURS AFTER BIRTH.
AND THIS IS TELLING US SOMETHING
VERY IMPORTANT.
FOOD IN THE GASTROINTESTINAL
TRACT IS VERY IMPORTANT IN TERMS
OF GROWTH OF THE INTESTINE, AND
I KNOW THAT IN CERTAIN INSTANCES
ESPECIALLY IN THE PRE-TERM
BABIES SOMETIMES WE DO NOT
PROVIDE FOOD INTO THE
GASTROINTESTINAL TRACT,
SOMETIMES FOR PROLONGED PERIODS
OF TIME, THIS CAN THWART THE
GROWTH OF THE INTESTINAL TRACT.
IT'S NOT JUST IN NUTRIENTS, BUT
IN THE GROWTH THESE BABIES ARE
GETTING, IT'S ALSO BIOACTIVE
INGREDIENTS, GROWTH HORMONES,
MICROBES, VARIOUS OTHER FACTORS
THAT ARE VERY IMPORTANT IN
GETTING THIS GROWTH.
NOW, WE HAVE THE DIGESTION,
ABSORPTION, ASSIMILATION
PROPERTIES OF THE
GASTROINTESTINAL TRACT.
AND THESE ARE REALLY DIFFERENT
PROCESSES.
DIGESTION OCCURS IN THE LUMEN,
ABSORPTION AT THE ENTEROCYTE
INTERFACE, AND ASSIMILATION
OCCURS IN THE ENTEROCYTE AND
BEYOND.
AND WE HAVE A TREMENDOUS AMOUNT
OF MATURATION THAT IS OCCURRING
IN THESE DIFFERENT PHENOMENA
DURING THE EARLY LIFE OF THE
BABY.
SO, DIGESTION MAY BE LIMITED IN
TERMS OF PANCREATIC OR CAROTID
GRAND SECRETIONS, ABSORPTION MAY
BE LIMITED IN TERMS OF ENZYMATIC
CAPABILITIES.
AND ASSIMILATION MAY BE LIMITED
BY TRANSPORTERS THAT ARE PRESENT
AT THE GASTROINTESTINAL SURFACE
AND ENTEROCYTE AND BEYOND.
WHAT ABOUT FORMULAS?
IN HUMAN MILK, THE MAJOR
CARBOHYDRATE IS LACTOSE, ALMOST
THE SOLE DIETARY CARBOHYDRATE IN
THE MILK.
EXCEPT FOR SOME HUMANS IT'S NOT
CONSUMED BY ADULTS.
ON THE OTHER HAND, NEONATES DO
NOT NORMALLY INGEST SUCROSE OR
STARCH BUT ADULTS OFTEN DO.
AND WHAT WE FIND IS THE
CARBOHYDRATE IN MANY FORMULAS?
IN SOME, WE DO HAVE LACTOSE, BUT
WE ALSO HAVE FORMULAS THAT
CONTAIN MORE OTHER CARBOHYDRATES
SUCH AS SUCROSE, MALTOSE,
TAPIOCA STARCHES, SOME OF THESE
ARE RELATIVELY COMPLEX
CARBOHYDRATES, AND IN THE
GASTROINTESTINAL TRACT THE
AMYLASE FROM THE PAROTID GLAND
ARE NOT DEVELOPED IN THE FIRST
MONTH OR TWO AFTER BIRTH, SOME
CARBOHYDRATES ARE NOT UTILIZED
TO FULL EXTENT BECAUSE OF THIS
DIGESTIVE IMMATURITY IN THE
GASTROINTESTINAL TRACT.
NOW, ONE OF THE ASPECTS ABOUT
LACTOSE, IF IT IS NOT FULLY
ABSORBED BY THE UPPER
GASTROINTESTINAL TRACT THIS
LACTOSE IS TAKEN INTO THE COLON,
HAVE YOU CERTAIN BACTERIA
ESPECIALLY LACTOBACILLUS, AND
SHORT CHAIN FATTY ACIDS, AND
THESE ARE VERY IMPORTANT FOR
PHYSIOLOGY.
FOR EXAMPLE, ONE OF THE SHORT
CHAIN FATTY ACIDS, BUTYRATE, IS
THE MOST IMPORTANT FUEL,
INCREASES PROLIFERATION,
DIFFERENTIATION, TIGHTENS
INTEREPITHELIAL JUNCTIONS TO
KEEP THE GASTROINTESTINAL TRACT
FROM HAVING LEAKINESS THAT
ACTUALLY IS THOUGHT TO RESULT IN
SEVERAL KINDS OF DISEASES.
OVER THE FIRST 1,000 DAYS, THIS
IS A PARADIGM OVER THE PAST
COUPLE YEARS THAT'S BECOME VERY
IMPORTANT, WE HAVE THE FETAL
LIFE AND MATERNAL FACTORS, AND
WE HAVE THE POST-NATAL FACTORS
ON THE RIGHT OF THE SLIDE.
AND DURING THESE 1,000 DAYS WE
HAVE THIS INTERACTION BETWEEN
NUTRITION, MICROBIOME, AND
EPIGENOME, SEVERAL OTHER OMICS.
NEONATAL AND INFANT NUTRITION
MAY INVOLVE HUMAN MILK, FORMULA
MILK, AND ALL OF THE THINGS, NOT
JUST MICROBES, BUT VARIOUS OTHER
COMPONENTS OF HUMAN MILK THAT
ARE PRESENT THAT ARE BIOACTIVE,
THAT WE NEED TO TAKE INTO
CONSIDERATION.
THIS IS GOING TO BE PART OF THE
WORKSHOP TODAY.
ALSO FACTORS SUCH AS HUMAN
GENOME AND OTHER ENVIRONMENTAL
FACTORS PLAY A ROLE.
NOW, IN TERMS OF THE INTESTINAL
MUCOSAL SYSTEM, THERE ARE
SEVERAL HUMAN MILK BIOACTIVES
THAT AFFECT MUCOSAL IMMUNITY.
MICROBES, WE'LL BE HEARING A LOT
ABOUT THOSE.
NEOGLOBULINS, OLIGOSACCHARIDES
AND LACTOSE, EXTRACELLULAR
VESICLES, miRNA.
WE HAVE A CRITICAL WINDOW
ESPECIALLY IN THE FIRST SIX
MONTHS AFTER BIRTH WHERE I AM
PRINTING OF IMMUNE CELLS OCCURS
AND THIS AFFECTS THE INDIVIDUAL
FOR THE ENTIRE LIFETIME.
THERE'S IMMUNOLOGIC MEMORY AND
TOLERANCE, ALSO SEVERAL KEY
IMMUNE CELLS SUCH AS DENDRITIC
CELLS, B CELLS, NATURAL KILLER
CELLS, ET CETERA.
ON THE CARTOON WE SEE THE
INTESTINAL LUMEN, AND WE SEE THE
INTESTINAL EPITHELIAL SURFACE.
THERE'S SEVERAL DIFFERENT CELL
TYPES THAT LINE THE EPITHELIAL
SURFACE.
ONE OF THE CELL TYPES IS
DENDRITIC CELL, THOUGHT TO BE
EXTREMELY IMPORTANT BECAUSE THIS
DENDRITIC CELL CAN SENSE WHAT'S
IN THE LUMEN THE INTESTINE,
CHANGING THE CELL SURFACE TO
INTERACT WITH UNDIFFERENTIATED
LIMB SO FIGHTS TO TURN THEM INTO
EFFECTOR T CELLS OR TOLERIZING T
CELLS WHICH CAN AFFECT THE
INDIVIDUAL FOR THE ENTIRE
LIFETIME.
SO, WHAT IS IN THE LUMEN OF THE
INTESTINE IS VERY IMPORTANT.
WE ALSO OVER THE PAST DECADE OR
SO HAVE BEGUN TO RECOGNIZE THAT
THERE ARE BACTERIA PRESENT IN
HUMAN MILK, AND THIS IS JUST
FROM SOME DATA FROM STUDIES DONE
AT UNIVERSITY OF IDAHO SEVERAL
YEARS AGO, 2011, AND IN THIS
PAPER THEY SHOWED THE DATA FROM
SEVERAL DIFFERENT MOTHERS, AND
YOU CAN SEE EACH ONE OF THESE
REPRESENTS THE DIFFERENT MOTHER,
AND THE DIFFERENT COLORS
REPRESENT MICROBES AT DIFFERENT
STAGES, ONE WEEK, TWO WEEKS,
FOUR WEEKS AFTER BIRTH.
WITHIN THIS MOTHER, MIGHT BE
ROBES ARE SIMILAR.
WITHIN THIS MOTHER, THE MICROBES
ARE SIMILAR.
BUT IF YOU LOOK AT THE DIFFERENT
MOTHERS, YOU SEE VERY DIFFERENT
MICROBIAL PATTERNS.
DOES THIS REPRESENT SOMETHING
THAT IS REALLY SPECIFIC FOR EACH
MOTHER?
AND IS THIS SOMETHING THAT WE
SHOULD BE CONSIDERING IN TERMS
OF PRECISION NUTRITION IN THESE
MOTHERS AND BABIES?
WELL, THE MICROBES IN MILK MAY
BE VERY IMPORTANT, BUT THERE ARE
OTHER OMICS, NOT JUST THE
MICROBIOME, THAT WE NEED TO
CONSIDER.
HERE IS A PARADIGM OR PARABLE, A
HINDU PARABLE THAT TALKS ABOUT
THE SIX BLIND MEN OF INDOSTAN,
EACH WAS ASKED TO FEEL A PORTION
OF THE ANIMAL, THIS ELEPHANT.
ONE FELT THE SIDE AND THOUGHT
THIS WAS A WALL.
ONE FELT THE TAIL AND THOUGHT
THIS WAS A ROPE.
ONE FELT THE TUSK AND THOUGHT
THIS WAS A SPEAR.
THEY GOT TOGETHER AND ARGUED.
AND NONE OF THEM HAD THE RIGHT
ANSWER.
BUT IF THEY ALL WOULD HAVE PUT
THEIR ANSWERS TOGETHER, AND
THOUGHT ABOUT THIS, THEY WOULD
HAVE COME UP WITH THE IDEA THIS
WAS AN ELEPHANT.
AND THIS IS WHERE WE ARE GOING
WITH MULTI-OMICS IN THE FUTURE.
AND THE PROBLEM WITH MULTI-OMICS
IS THAT THE DATA THAT IS
GENERATED WITH MULTI-OMICS IS
HUGE BUT NOW WE'RE ALSO
DEVELOPING THESE BIOINFORMATIC
TECHNOLOGIES BASED ON DEEP
LEARNING AND ALSO PREDICTIVE
ANALYTICS, ARTIFICIAL
INTELLIGENCE, THAT ARE GOING TO
BE VERY IMPORTANT AND WILL HELP
US IN THE FUTURE FOR PRECISION
MEDICINE.
SO HERE'S JUST A PARADIGM USED
FOR CANCER PATIENTS.
YOU TAKE SOME OMICS, GENOMICS,
TRANSCRIPTOMICS, PROTEOMICS, AND
USE ARTIFICIAL INTELLIGENCE.
YOU'RE ABLE TO TELL WHAT KIND OF
DIFFERENCES OCCUR IN INDIVIDUAL
WHO DEVELOPS CANCER VERSUS A
HEALTHY INDIVIDUAL.
WE CAN DO SOMETHING VERY SIMILAR
WITH OUR BABIES.
WE CAN LOOK AT THE OPTIMAL
NUTRITIONAL HEALTH, WITH A
SCORING SYSTEM, AND UTILIZE
MACHINE LEARNING AND PREDICTIVE
ANALYTICS AND LOOK AT BABIES WHO
ARE NOT DEVELOPING IN A HEALTHY
WAY.
AND WE CAN MAKE COMPARISONS,
USING MULTI-OMICS, NETWORK
ANALYTICS, AND BIOMARKER
DISCOVERY, THIS WILL HELP US IN
THE FUTURE WITH PERSONALIZED
MICROBIAL AND THERAPEUTIC
INTERVENTIONS.
WHAT ARE CHALLENGES?
HERE IS A BABY WHO IS BURPING UP
FOOD, GASTROESOPHAGEAL REFLUX,
VERY COMMON PROBLEM IN ALL KINDS
OF BABIES.
VERY VEXING FOR THE PARENTS.
AND THIS IS ONE OF THE
CHALLENGES THAT WE HAVE.
HUMAN MILK OR MILKFORMULA ARE
ABLE TO HELP WITH REFLUX BUT WE
MAY BE ABLE TO FIND WAYS TO HELP
WITH GASTROESOPHAGEAL REFLUX.
HERE IS ANOTHER CLINICAL
CHALLENGE, COLIC.
BABIES SCREAMING AND CRYING AND
WAKING THEIR PARENTS UP AT
NIGHT.
WE'RE BEGINNING TO RECOGNIZE
THAT THERE MAY BE SOME
COMPONENTS OF HUMAN MILK THAT
MAY BE HELPFUL IN COLIC, AND
THAT MICROBIAL ECOLOGY OF
GASTROINTESTINAL TRACT MAY BE
IMPORTANT.
SO, WE HAVE A LOT TO LEARN, THIS
IS ONE OF THE CHALLENGES.
I'D LIKE TO END WITH A QUOTE
FROM MARCUS AURELIUS, IMPEDIMENT
TO ACTION ADVANCES ACTION.
WHAT STANDS IN THE WAY BECOMES
THE WAY.
THANK YOU FOR YOUR ATTENTION.
>> THANK YOU VERY MUCH.
GREAT TALK.
I DO ENCOURAGE EVERYONE ONLINE
WHO IS WATCHING VIA VIDEOCAST TO
SUBMIT QUESTIONS TO THE IN-BOX
WE'RE MONITORING.
AND DR. NEU, ONE QUESTION THAT
CAME IN, CAN YOU COMMENT ABOUT
THE POSSIBILITY AND EFFECTS OF
ADDING (INDISCERNIBLE) ON G.I.
TRACT DEVELOPMENT.
>> WE DON'T KNOW THE DOSE OF
BUTYRATE THAT MAY BE HELPFUL.
SEVERAL YEARS AGO WE DID SOME
STUDIES LOOKING AT TYPE 1
DIABETES AND BUTYRATE, TO DAMP
DOWN EXTRACELLULAR, CELLULAR
JUNCTION LEAKINESS AND THOUGHT
THIS MAY BE SOMETHING THAT COULD
BE HELPFUL BUT HIGHER DOSES HARM
THE ANIMAL SO I THINK WE HAVE TO
BE VERY CAREFUL CONSIDERING
PUTTING BUTYRATE RIGHT INTO
FORMULAS.
WE HAVE TO HAVE THE RIGHT DOSE.
>> AND TO FOLLOW UP ON THAT,
JOE, THE QUESTION CAME IN, DOES
ORAL BUTYRATE MAKE IT INTO THE
DISTAL INTESTINE, OR DO WE KNOW?
>> IT SHOULD.
IT SHOULD, BECAUSE I DON'T KNOW
OF THE DEGRADEATORY PATHWAY.
WITH THAT WE'RE AHEAD OF
SCHEDULE.
THEN WE WILL BUILD SOME TIME FOR
QUESTIONS AND ANSWERS.
WE'LL MOVE TO THE NEXT SPEAKER,
DR. MEGAN AZA D.
>> THANKS, DREW.
I'LL GET MY SLIDES UP.
ALL RIGHT.
WELL, I'M EXCITED FOR ALL THE
REST OF THE TALKS.
IT'S GRADE TO HAVE SO MANY
EXPERT MILK SCIENTISTS TOGETHER
IN ONE VIRTUAL ROOM.
SO I WAS TASKED WITH SPEAKING
ABOUT THE MICROBIOME AND ITS
NORMAL DEVELOPMENT IN HEALTHY
INFANTS, HOW MILK RESEARCH AND
COMPONENTS ARE IMPORTANT FOR
THAT.
SO I WILL START BY SHOWING MY
RESEARCH FUNDING SOURCES, AND I
HAVE NO PARTICULAR CONFLICTS FOR
TODAY'S TALK.
KEY MESSAGES AND COME BACK AT
THE END.
FIRSTLY, THE MICROBIOME IS
IMPORTANT FOR HEALTH.
PARTICULARLY DURING INFANCY.
SECONDLY DIET SHAPES THE
MICROBIOME.
AND THINKING ABOUT INFANTS,
HUMAN MILK EVOLVED TO FEED
IMFANS AND THEIR MICROBES,
FEEDING NOT JUST THE BABY BUT
THE DEVELOPING MICROBIOME.
AS WE HEARD IN THE LAST TALK
MILK IS COMPLEX, DYNAMICS,
PERSONALIZED, MANY COMPONENTS
INFLUENCE THE MICROBIOME.
AND THERE'S A LOT WE STILL DON'T
UNDERSTAND.
MICROBIOME SCIENCE IS STILL KNEW
IN THE WAY IT'S BEING STUDIED
AND INTERACTION OF MINIMUMMING
MILK WITH MICROBIOMING E IS A
NEW FIELD.
BEFORE I GET TO THE MILK, THIS
IS INFOGRAPHIC THAT SUMMARIZES
THE DIFFERENT ROLES OF GUT
MICROBE.
ONE, THEY MAKE VITAMINS
INCLUDING B-12, K, FOLATE, WE
CAN'T DO THAT OUR OWN.
IMPORTANTLY FOR INFANTS,
TEACHING THE IMMUNE SYSTEM TO
TELL FRIENDS FROM FOES.
MY RESEARCH HAS FOLKS ON THE
MICROBIOME AND ALLERGIES, AND
WE'LL MORE ABOUT THAT.
EARLY IN LIFE THE IMMUNE SYSTEM
NEEDS TO LEARN WHAT TO REACT TO
AND WHAT TO BE OKAY WITH.
GUT MICROBES PLAY AN IMPORTANT
ROLE UNTIL THAT PROCESS.
WHEN THE GET MICROBIOME DOESN'T
DEVELOP PROPERLY IN INFANCY IT
CAN RESULT IN ALLERGIES OR
MISFIRINGS AND AUTOIMMUNE
DISEASES.
MICROBES PRODUCE IMPORTANT
MOLECULES THAT CAN TRAVEL AROUND
THE BODY, IT'S NOT JUST THE GUT.
YOU HEARD ABOUT GUT-BRAIN
ACCESS, THIS INVOLVES MICROBIAL
METABOLITES PRODUCED IN THE GUT
ABSORBED AND TRAVELING TO OTHER
BODY SITES AND HELP DEFEND
AGAINST PATHOGENS THAT MIGHT
CAUSE INFECTION.
TWO PEOPLE EATING THE SAME DIET
COULD GAIN OR LOSE DIFFERENT
AMOUNTS OF WEIGHT FROM THE SAME
DIET BASED ON THEIR DIFFERENT
MICROBIOMES THAT HARVEST
DIFFERENT AMOUNTS OF CALORIES
FROM THE SAME FOOD HAVING
IMPLICATIONS FOR OBESITY AND
STUNTING AND WASTING WHERE
MALNUTRITION IS A PROBLEM.
GUT MICROBES HELP PRODUCE
SEROTONIN, IMPORTANT FOR OPTIMAL
GUT FUNCTION.
THIS IS A VERY HIGH LEVEL VIEW.
WE ALL KNOW THE GUT MICROBIOME
IS IMPORTANT.
THE OTHER THING TO KNOW OUR
MICROBIOME CHANGES ACROSS THE
LIFESPAN, UNLIKE OUR GENES, OUR
MICROBIOME, THE GENES THAT COME
INSIDE OUR MICROBES, CAN CHANGE
DRAMATICALLY ACROSS THE LIFESPAN
DEPENDING ON JUST NORMAL PROCESS
OF AGING, ALSO IF WE DO THINGS
LIKE TAKE ANTIBIOTICS.
SO OF COURSE FOR NOW WE'RE
INTERESTED IN FIRST THOUSAND
DAYS OF LIFE FOR THAT PERIOD OF
INFANCY, YOU CAN SEE OVERALL
SHIFT IN THE MICROBIOME, LOOKING
AT THE RICHNESS AND DIVERSITY OF
THE MICROBIOME AS A WHOLE, THAT
HAPPENS OVER TIME.
THIS PERIOD OF THE FIRST
THOUSAND DAYS, FIRST TWO YEARS,
IS A PERIOD OF RAPID CHANGE AS
COMPARED TO THE REST OF OUR LIFE
WHEN THE CHANGE IS MUCH LESS
RAPID.
THE FACTORS THAT INFLUENCE GUT
MICROBIOME CHANGE ACROSS THE
LIFESPAN.
FOR TODAY I'M GOING TO FOCUS ON
DIET IN THAT FIRST THOUSAND
DAYS, PERIOD.
WHICH PRIMARILY IS BREAST MILK
OR FORMULA.
THESE ARE DATA FROM MY RESEARCH
IN THE CHILD COHORT STUDY,
NATIONAL PREGNANCY IN CANADA,
OVER 3,000 FAMILIES WITH
CHILDREN BORN AROUND 2010, STILL
FOLLOWING TODAY.
SO LONGER THE STUDY GOES, THE
MORE WE CAN LEARN ABOUT
LONG-TERM IMPACT OF CHANGES
RELATED TO MICROBIOME.
SO THESE ARE DATA WHERE WE
LOOKED AT THE MICROBIOTA AT A
YEAR OF AGE CLASSIFIED ON
INFANTS NOT BREASTFED, PARTIALLY
BREASTFED OR EXCLUSIVELY
BREASTFED.
YOU CAN SEE VERY CLEAR
DIFFERENCES IN DIFFERENT TYPES
OF METHODS WE USE TO MEASURE THE
MICROBIOME.
SO HERE LOOKING AT THE SHANNON
DIVERSITY INDEX, YOU CAN SEE
HIGHEST DIVERSITY IS FOUND IN
INFANTS THAT WERE NOT RECEIVING
BREAST MILK, LOWEST DIVERSITY
FOUND IN INFANTS RECEIVING
EXCLUSIVELY BREAST MILK.
PARTIALLY BREASTFED INFANTS IN
THE MIDDLE.
SIMILAR TREND LOOKING AT
DIFFERENT METRIC, MICROBIAL AGE.
DOWN HERE WE HAVE COORDINATE
ANALYSIS WHICH SHOWS COMPOSITION
OF THE MICROBIOME, EACH DOT IS
ONE INFANT, CLOSER TWO DOTS ARE
TOGETHER THE MORE SIMILAR THE
MICROBIOME.
YOU IS EESPECIALLY IN THE
NON-BREASTFED AWAY FROM THE
OTHER BREASTFED INSTANTS.
THIS PAINTS A PICTURE THAT
FORMULA FEEDING SIGNIFICANTLY
ALTERS THE MICROBIOME IN EARLY
LIFE.
THOSE METRICS ARE ALL ABOUT
OVERALL MICROBIOME DIVERSITY,
COMPOSITION, AGE, WE ALSO COULD
LOOK AT SPECIFIC MICROBES.
AND SO IN THIS INSTANCE WE
LOOKED THE BACTERIA NON-TO BE
BENEFICIAL IN THE INFANT GUT,
AND YOU CAN SEE WITH MORE
EXCLUSIVELY BREASTFEEDING THERE
ARE HIGHER PROPORTION OF
BIFIDOBACTERIA.
EXCLUSIVELY BREASTFED IS IN TWO
GROUPS, EXCLUSIVELY FROM BIRTH,
AND VERSUS THOSE THAT RECEIVED A
LITTLE BIT OF FORMULA, ONE
BOTTLE IN THE HOSPITAL, AND THEN
EXCLUSIVELY BREASTFED.
WE WERE ACTUALLY SURPRISED TO
SEE A DIFFERENCE.
WE DIDN'T SEE DIFFERENCE IN
OVERALL COMPOSITION, ON THE
LEFT, BUT DID SEE SPECIFICALLY
AT BIFIDOBACTERIA, BOTTLE BABIES
HAD LOWER PROPORTIONS OF
BIFIDOBACTERIA COMPARED TO TRULY
EXCLUSIVELY BREASTFED BABIES,
STILL WORKING TO UNDERSTAND IF
THIS HAS A HEALTHY IMPACT BUT WE
SEE A MICROBIOME IMPACT.
THIS MICROBIOME MEASUREMENT IN
THIS CASE MADE AT 3 TO 4 MONTHS
AFTER THE SINGLE EXPOSURE
BRIEFLY TO FORMULA.
THESE ARE IMPORTANT THINGS TO
CONSIDER IN TERMS OF DIETARY
EXPOSURES TO THE INFANT
MICROBIOME.
MUCH LARGER STUDY WHICH I LOVE
IS FEATURED ON THE COVER OF
"NATURE" A COUPLE YEARS AGO,
NUMBER OF SAMPLES ANALYZED.
THEY HAD MANY EXAMPLES AND
LOOKED AT IMPACT OF
BREASTFEEDING IN RELATION TO
OTHER FACTORS.
BREASTFEEDING AND FORMULA
FEEDING ARE IMPORTANT BUT HOW
IMPORTANT ARE THEY, THIS STUDY
GIVES REALLY NICE CONTEXT.
LOOKING AT TWO TIME PERIODS,
THREE TO SIX, AND SEVEN TO TEN
MONTHS, MATERNAL BMI, METHOD OF
BIRTH, MOM TAKING PROBIOTICS,
ANTIBIOTICS, YOU CAN SEE THAT
BREAST MILK IS BY FAR THE MOST
IMPACTFUL FACTOR SHAPING INFANT
MICROBIOME, ORDERS OF MAGNITUDE
HIGHER, PARTICULARLY DURING THE
FIRST FEW MONTHS.
THIS HITS HOME HOW IMPORTANT
BREASTFEEDING IS FOR THE INFANT
MICROBIOME.
WE DID FOLLOW THE BABY UP UNTIL
40 MONTHS OF AGE, THE PINK BAR
IS SHRINKING, IMPACT OF BREAST
MILK ON THE MICROBIOME
COMPOSITION WANED OVER TIME.
THAT MAKES SENSE, STARTING TO
BE EXPOSED TO MORE THINGS LIKE
FURRY PETS AND THINGS OUTSIDE AS
THEY CRAWL ON THE -- AS THEY
CRAWL AROUND.
THE IMPACT OF BREAST MILK WANES
OVER TIME BUT IT'S IMPORTANT TO
REMEMBER JUST BECAUSE THE
MICROBIOME RECOVERS DOESN'T MEAN
THAT THERE HASN'T BEEN A
PERMANENT IMPACT, A LONG TERM
IMPACT ON HEALTH.
THIS PAPER WAS DONE IN MICE,
USING ANTIBIOTICS BUT FORMULA
CAN ALSO DISRUPT THE MICROBIOME.
LIMITED TO EARLY LIFE, JUST
NEONATAL PERIOD OR A FEW WEEKS
EARLY IN LIFE, THEY FOUND AFTER
THEY STOPPED TREATING WITH
ANTIBIOTICS THE MICROBIOME
RECOVERED BUT THEY SAW PERMANENT
EFFECTS ON METABOLISM AND BODY
COMPOSITION OF MICE, EVEN WHEN
ADULTS, MORE LIKELY TO BECOME
OBESE AND HAD METABOLIC
DIMENSIONS.
JUST BECAUSE WE SEE IT RECOVER
DOESN'T MEAN THERE HASN'T BEEN
IMPORTANT AND PERMANENT IMPACT
ON THE MICROBIOME AND RELATED
HEALTH OUTCOMES.
THE SECOND BOX, THE IMPACT OF
BREASTEL MILK WANES OVER TIME IN
THE TEDDY STUDY BUT THEIR
FUNCTION COULD CHANGE IN THE
ABSENCE OF BREAST MILK.
IN THIS STUDY WE FOUND THAT
HUMAN MILK OLIGOSACCHARIDES
NEUTRALIZATION GENES ARE FOUND
IN CERTAIN INFANT GUT MICROBES,
SO THAT MAKES SENSE, GUT
MICROBES ARE READY TO CONSUME
HUMAN MILK OLIGOSACCHARIDES, AND
MIGHT STILL BE AROUND AFTER
WEANING, AND I THINK WE HAVE TO
REMEMBER JUST LOOKING AT WHAT
MICROBES ARE THERE ISN'T GIVING
US THE WHOLE PICTURE SO THIS
REMOVAL OF BREAST MILK IF NOT
CHANGING THE COMPOSITION OF
MICROBES COULD BE CHANGING THEIR
FUNCTION.
WE'VE TALKED ABOUT MICROBES.
I'VE MENTIONED OLIGOSACCHARIDES,
YOU'LL HEAR ABOUT THEM LATER,
WHAT ARE OTHER COMPONENTS?
IMPORTANT MICRO AND
MACRONUTRIENTS, MANY THINGS ON
TOP OF OF THAT THAT AREN'T FOUND
IN FORMULA BECAUSE THEY ARE
PERSONALIZED, UNIQUE TO HUMAN
MILK.
AND THIS GIVES THE SAME PICTURE.
TWO OF MY FAVORITE ELEMENTS, PRO
ANTIBIOTIC BACTERIA AND
OLIGOSACCHARIDES.
SOME DO HAVE BACTERIA AND
OLIGOSACCHARIDES, IT'S TRUE, BUT
HUMAN MILK CONTAINS HUNDREDS OF
STRAINS OF BACTERIA AND FORMULAS
CONTAIN ONE OR A FEW.
HUMAN MILK CONTAINS OVER 100
OLIGOSACCHARIDES, OTHERS INCLUDE
ONE OR A FEW.
YOU'LL HEAR MORE ABOUT THAT
LATER IN THE WORKSHOP.
I THINK IT'S IT'S GOOD TO
REMEMBER WE STILL HAVE
QUESTIONS.
I'VE GOT ASTERISKS HERE.
WE'RE STILL LEARNING IF MILK
MICROBES, WE KNOW THEY ARE
PRESENT BUT DO THEY COLONIZE THE
INFANT GUT, MOUTH, NOSE, SO ON?
WE'RE STILL UNDERSTANDING HOW OR
IF EACH SHAPES THE INFANT GUT
MICROBIOME SO THEY CAN FUNCTION
AS SUBSTRATES BUT HOW DO THEY
WORK IS SOMETHING WE'RE LEARNING
ABOUT.
DO THEY INTERACT WITH THE GUT
EPITHELIUM AND HOW DOES THAT
WORK?
AND IS THERE A CORE MILK
MICROBIOME THAT IS COMMON TO ALL
WOMEN OR IS IT TOTALLY
PERSONALIZED?
AND WITH HMOs IS THERE CORE
GLYCOME, SO THESE QUESTIONS WILL
BE ASKED LATER ON.
ONE LITTLE BIT OF DATA FROM THE
CHILD COHORT STUDY THAT I
PARTICIPATED IN TO TRY AND
ADDRESS THAT FIRST QUESTION,
WHETHER MILK MICROBES COLONIZE
THE INFANT GUT, IN COLLABORATION
WITH STUART TURVEY AND COMBINED
DATASETS FROM THE SAME
MOTHER-INFANT DIET, THEY LOOKED
AT MICROBIOME, MY TEAM LOOKED AT
THE MILK MICROBIOME.
WHEN WE OVERLAID THE DATA WE
FOUND THAT THE MILK MICROBES
WERE DIFFERENT FROM GUT
MICROBES, THEY ARE TWO DIFFERENT
NICHES.
WE FIND THE SHORT LIST OF A
DOZEN SHOWN HERE THAT SEEM TO BE
SHARED BETWEEN MILK AND GUT.
AND THEY WERE POSITIVELY
CORRELATED BETWEEN MILK AND GUT
SAMPLES FROM THE SAME
MOTHER-INFANT PAIRS.
NOT ALL MICROBES MAY HAVE
EVOLVED TO BE TRANSFERRED
TRANSFERRED FROM MILK TO GUT.
TWO IDENTIFIED EARLIER BY THE
TEAM AS BEING MICROBES THAT
PROTECT AGAINST ATP AND ASTHMA,
MICROBES MAY MAY ALSO HAVE
IMPORTANT AND BENEFICIAL HEALTH
ROLE AND COLONIZE THE GUT.
IF WE LOOK AT WHAT'S BEING ADDED
WE DON'T THINK ANY WERE ON THIS
LIST.
WE HAVE TO LEARN WHICH ARE THE
IMPORTANT MICROBES TO BE
PROVIDED TO INFANTS.
SO, WE LOOKED AGAIN AT TAKING A
STEP BACK LOOKING AT THE WIDER
CONTEXT HOW IMPORTANT ARE MILK
BACTERIA AND HMOS SHAPING INFANT
GUT MICROBIOME?
THEY BOTH TURNED UP AS BEING
SIGNIFICANTLY IMPORTANT IN
PREDICTING GUT MICROBIOME
COMPOSITION AND THE OTHER ITEMS,
TWO TO THREE COMPARED TO OTHER
KNOWN FACTORS, C-SECTION AND
ANTIBIOTICS THAT WE KNOW IMPACT
MICROBIOME, SIMILAR LEVEL OF
EFFECT.
HE'S ARE IMPORTANT COMPONENTS
SHAPING THE MICROBIOME.
WE TALKED ABOUT MILK BACTERIA
AND HMOs BUT WE HAVE A LOT TO
LEARN ABOUT OTHER MILK
COMPONENTS.
THERE ARE SOME DATA SUGGESTING
OTHER MILK COMPONENTS ALSO SHAPE
GUT MICROBIOME, SO THESE INCLUDE
IMMUNOGLOBULIN A, WHICH COMBINED
IN MILK AND GUT MICROBES, LEPTIN
IS ASSOCIATED, MILK
EXTRACELLULAR VESICLES, AND IRON
IN MILK AS A MICRONUTRIENT MIGHT
BE RELEVANT.
AND THEN FATTY ACIDS FOUND AT
HIGH ABUNDANCE IN HUMAN MILK
SHOWN TO CORRELATE WITH THE MILK
MICROBIOTA.
A QUICK NOTE ON FORMULA TRIALS,
THE MICROBIOME IS NOT OFTEN
REPORTED, SOMETHING TO THINK
ABOUT GOING FORWARD.
OF COURSE, APPRECIATE THAT
GROWTH AND HEALTH OUTCOMES ARE
TOP OF MIND.
WHICH ONES ARE THE MOST
MEANINGFUL?
WE DON'T NECESSARILY KNOW THE
ANSWER TO THAT.
I'VE COVERED A FEW IN THIS
PRESENTATION, SO DIVERSITY,
MICROBIOME AGE, PRESENCE OR
ABUNDANCE, SOME TRIALS LOOK AT
OVERALL SIMILARITY TO BREASTFED
INFANTS.
I'M OPEN TO OPINIONS ON WHICH IS
THE BEST WAY TO ANALYZE THE
MICROBIOME TO KNOW IF IT'S GOOD
OR HEALTHY.
PARTING THOUGHTS ON THE
MICROBIOME, FORMULA IS LACKING
MANY HUMAN COMPONENTS AND BOTH
ARE RELEVANT.
IT'S IMPORTANT TO THINK BOTH
WHAT DO WE NEED TO PROVIDE AND
WHAT TO AVOID IDEALLY.
I THINK IT TAKES SOME THOUGHT TO
KNOW WHICH ARE THE MOST
MEANINGFUL.
AND ALSO IT'S NOT JUST THE GUT.
INFANT FEEDING AFFECTS OTHER
MICROBIOME.
WE STARTING IN THE CHILD STUDY
TO LOOK AT ORAL MICROBIOME AND
MUCOSAL MICROBIOME OF INFANTS,
MORE DIRECTLY IN CONTACT WITH
HUMAN MILK, ALSO HAVE IMPORTANT
ROLE IN INFANT HEALTH INCLUDING
DEVELOPMENT OR PREVENTION OF
ASTHMA AND ALLERGIES.
SO THIS WAS MY ORIGINAL SLIDE.
I'LL END ON IT.
KEY MESSAGES THAT THE MICROBIOME
IS CLEARLY IMPORTANT TO HEALTH
ESPECIALLY IN INFANTS.
DIET SHAPES THE MICROBIOME.
FINALLY MILK IS COMPLEX,
DYNAMIC, PERSONALIZED,
COMPRISING MANY COMPONENTS,
THERE'S A LOT WE DON'T
UNDERSTAND ABOUT ALL OF THIS.
I'D BE HAPPY TO TAKE QUESTIONS
NOW OR LATER, WHATEVER DREW
SAYS.
HE'S THE BOSS.
>> I'LL INVITE APRIL TO THE
SHOW.
>> MY COMPUTER IS SLOW TODAY.
THANK YOU FOR THE GREAT TALK, I
HAD SOME QUESTIONS AND I SAW
THERE ARE MANY QUESTIONS FROM
THE AUDIENCE.
IT'S GREAT WE HAVE SO MUCH TIME
BECAUSE THESE QUESTIONS COVER
THE GAMUT.
FIRST PERSONALIZATION OF MILK TO
THE INFANT, WONDERING IF SOME OF
THIS HAS TO DO WITH AUREOLAR
MICROFLORA IN ADDITION TO
VAGINAL?
AND ALSO WOUND ERIC FROM THE
AUDIENCE IF -- WONDERING,
EVIDENCE ABOUT PERSONALIZATION
OF MILK TO THE INFANT.
>> , YES MIGHT BE ROBES ON THE
MOTHER'S SKIN, BREAST, MAKE IT
TO THE INFANT, WE HAVE TO BE
CAREFUL WE DON'T LUMP ALL BREAST
MILK FEEDING IN ONE BUCKET.
PUMPED MILK, A COMMON PRACTICE,
IS NOT THE SAME AS FEEDING AT
THE BREAST BECAUSE YOU DON'T
HAVE SKIN TO SKIN CONTACT WHERE
MICROBES ARE EXCHANGED, ALSO
WE'RE SEEING MORE EVIDENCE THAT
METHOD OF FEEDING IS RELATED TO
MICROBIOME COMPOSITION AND
DIRECT EVIDENCE PRESENTED THIS
YEAR THAT MICROBES FROM ORAL
CAVITY COLONIZING THE MILK.
THAT'S PART OF THE
PERSONALIZATION IN TERMS OF
MICROBES MOM IS PROVIDING IN
MILK THROUGH HER SKIN TO HER OWN
BABY, THE SECOND PART
PERSONALIZATION OF MILK IN
GENERAL, THINKING ABOUT -- LET
ME PULL UP THE EXACT TEXT OF THE
QUESTION.
THERE'S BEEN NICE RESEARCH ON
SOURCE TRACKING OF MICROBES IN
THE INFANT GUT TO LOOK AT WHAT
PROPORTION SEEM TO COME FROM THE
MOTHER'S MILK VERSUS MOTHER'S
SKIN VERSUS THE MOTHER'S GUT OR
VAGINAL TRACT, ONE WAS PUBLISHED
IN PEDIATRIC JAMA A COUPLE YEARS
AGO SHOWING CONTRIBUTION FROM
ALL OF THOSE.
>> WITH PERSONALIZATION WITH
RELATIONSHIP TO FEEDING IF YOU
HAVE, FOR EXAMPLE, DIFFERENCES
ACROSS INFANT OR MOTHER-INFANT
DYADS RELATED TO AUREOLAR OR
VAGINAL, OTHER ASPECTS OF
FEEDING ENVIRONMENT IF THAT
WOULD ACTUALLY CHANGE THE
NUTRIENT UPTAKE UPTAKE WITH
MILK OUT OF THE BREAST AND HOW
INFANT UTILIZES MILK BASED ON
BACTERIA PRESENT TO AID
DIGESTION.
AND MATERNAL AND INFANT GENETIC,
SECRETER STATUS INFLUENCING MILK
COMPOSITION, WE'LL HEAR MORE
LATER, INFANTS ALSO HAVE ARE NOT
PRODUCING MILK BUT SECRETER
STATUS INFLUENCES GUT EPITHELIUM
AND WHICH MICROBES WILL BE
ENRICHED, SO THERE'S A
PERMANENTIZATION FROM THAT.
WE KNOW ALSO HMOs ARE NOT ONLY
PRODUCING MILK SO INFANTS COULD
CONSUME IN UTERO AND PERHAPS
PRIMED TO RECEIVE THEIR OWN
MOTHER'S MILK WITH SIMILAR HMO
CONTENT, THESE ARE ALWAYS WAYS
MILK IS PERSONALIZED THROUGH
GENETICS, THROUGH THE
ENVIRONMENT.
>> IS THERE EVIDENCE MILK
LEVEL -- DO MILK LEVELS CHANGE
AS INFANT STATUS CHANGES?
PERHAPS CAN MILK RESPOND TO --
CAN MILK CHANGE TO ADDRESS
NUTRITIONAL NEEDS OF THAT
PARTICULAR INFANT?
>> GREAT QUESTION.
GETTING AWAY FROM THE MICROBIOME
TOPIC.
I DON'T WANT TO ANSWER ALL THE
QUESTIONS OTHER PEOPLE HAVE.
AS A GENERAL ANSWER, YES, THE
CONTENT OF MILK CHANGES OVER
TIME, SO OVER LACTATION, ALSO
LIKE FROM MORNING TO NIGHT FOR
SOME COMPONENTS, THE BABY GROWS,
EVEN WITHIN ONE FEEDING, THERE'S
LOTS OF DYNAMICS IN MILK TO WHAT
EXTENT IT IS CHANGING IN
RESPONSE TO SPECIFIC NEEDS OF
THE INFANT.
I THINK IT'S ANOTHER ONE OF THE
QUESTIONS WE'RE STILL LEARNING
ABOUT.
THE RESEARCH I'M MORE FAMILIAR
WITH IS IMMUNITY, IS BABY HAS
INFECTION, IS THAT COMMUNICATED
BACK TO THE MOM, DOES SHE KIND
OF CHANGE HER IMMUNE FACTOR
PRODUCTION NUTRIENT, I'M NOT
SURE ABOUT THAT ONE BUT OTHERS
MIGHT HAVE BETTER KNOWLEDGE THAN
ME.
>> GREAT.
AND THEN LET'S MOVE A LITTLE --
WELL, SORT OF PLACING A
DIFFERENT EMPHASIS REGARDING THE
FEEDING OF THE MICROBIOME IN
FANS BASED ON MODE OF DELIVERY
OR FEEDING I WANTED TO TOUCH
BACK ON SOMETHING YOU SAID A
WHILE AGO ABOUT BOTTLE FEEDING
OF BREAST MILK VERSUS DIRECTLY
FROM THE BREAST, WHETHER OR NOT
DIFFERENCES IN THE MICROBIOME OF
INFANTS FED EXPRESSED EXPRESSED
VERSUS DIRECT LY FROM THE
BOTTLE, EXPRESSION,
REFRIGERATION, WHAT'S GOING ON
THERE?
>> YEAH, GREAT QUESTIONS.
SO WE WERE ABLE TO DIRECTLY
STUDY THOSE ISSUES IN OUR COHORT
BUT THIS IS -- IS IT ABOUT THE
WAY THE MILK IS STORED?
WE'VE DONE A LITTLE BIT OF WORK
CAN YOU RECOVER MICROBES AFTER
STORING AND DIFFERENT
TEMPERATURES, THAT'S ONE
POSSIBILITY.
ALSO POSSIBLE THAT OTHER
BACTERIA BEING INTRODUCED
THROUGH THE PUMP, SO ACTUALLY MY
FORMER POSTDOC SARAH REYES
PUBLISHED A PAPER THIS WORK, I
CAN LINK IT IN THE CHAT, WHERE
SHE DID A RANDOMIZED TRIAL OF
PUMPING, MOMS WHO PUMP, HAD THEM
PUMP HOW THEY NORMALLY DO IT OR
WITH A STERILE HOSPITAL GRADE
PUMP AND FOUND VERY BIG
DIFFERENCES IN THE MICROBIOME OF
MILK OF MOMS PUMPING IN TWO
CIRCUMSTANCES.
SHE WENT FURTHER TO LOOK AT
RELATIONSHIPS BETWEEN THE WAY
THE MOMS WERE STORING AND
CLEANING PUMPS, SO DEFINITELY
THAT HAD EFFECT ON MICROBIOME IN
THE MILK PASS TO THE BABIES.
WHAT IMPACT THAT HAS ON THE
BABY'S MICROBIOME SUN KNOWN BUT
CERTAINLY THERE'S LOTS OF
QUESTIONS AROUND PUMPING AND THE
MICROBIOME AND HOW IS IT
IMPACTING MILK.
AND ASIDE FROM MICROBES COULD
BE AFFECTED STORAGE, HEATING,
AND IN OUR COHORT PUMPING IS NOT
AS COMMON BECAUSE MOST ARE ON A
YEAR MATERNITY LEAVE SO MOMS
WEREN'T NECESSARILY PUMPING A
LOT, THE DIFFERENCES WE'VE SEEN
IN TERMS OF RELATIONSHIPS WITH
ASTHMA, MICROBIOME, SHARING OF
MIKE ROCKIES ARE -- RE --
MICROBES ARE UNDERESTIMATED.
>> WOMEN WOULD BE INTERESTED IN
HEARING IMPROVEMENTS TO THE WAYS
THEY ARE EXPRESSING OR STORING
THE MILK.
I THINK ANOTHER QUESTION HAS
COME IN ABOUT WHETHER OR NOT THE
BREASTFEEDING -- SORT OF
RELATED, RIGHT?
BREASTFEEDING OR FEEDING
EXPRESSED BREAST MILK CAN
OVERCOME, ALTHOUGH I DON'T LIKE
THAT TERM, OVERCOME IMPACT OF
MODE OF DELIVERY, CASAREAN OR
VAGINAL, I CAVEAT THESE, A LOT
OF PROCEDURES ARE OUTSIDE THE
MOTHER'S CONTROL AND I ALWAYS
HESITATE TO IMPLY SOMETHING
COMPLETELY OUT OF A MOTHER'S
CONTROL COULD HAVE A NEGATIVE
IMPACT ON THE LIFE OF THEIR
INFANT.
SO WITH THAT IN MIND, HOW DO YOU
SEE THE ROLE OF BREAST MILK
FEEDING EITHER BOTTLED OR AT THE
BREAST ALTERS MICROBIOME
DEVELOPMENT OF THOSE BABIES?
>> GREAT QUESTION.
I ALSO LOVE YOUR CAVEAT.
I'LL MAKE A CAVEAT TO THE LAST
DISCUSSION.
WE'RE NOT SAYING PUMPED MILK IS
BAD.
SOME RESEARCH HAS BEEN SPUN THAT
WAY IN THE MEDIA WHICH I REGRET.
WE KNOW FOR A LOT OF MOMS IT'S
THE ONLY WAY THEY CAN PROVIDE
BREAST MILK, IT'S REALLY GOOD,
BUT IT'S IMPORTANT RESEARCH TO
DO BECAUSE LIKE WE SAID IF WE
FIND OUT IT'S SOMETHING ABOUT
THE WAY MILK IS STORED OR PUMPED
OR NOT HAVING SKIN TO SKIN
CONTACT, IT'S ADVICE WE CAN GIVE
TO MOMS.
NEXT QUESTION ABOUT VAGINAL OR
C-SECTION DELIVERY, C-SECTION IS
SOMETIMES NECESSARY, OUT OF
MOM'S CONTROL BUT IT HAS AN
IMPACT ON INFANT MICROBIOME AND
FIRST MICROBES SEEDING THAT
INFANT, AND YES WE HAVE SHOWN IN
OUR STUDY AND OTHERS NOW TOO
THAT THAT IMPACT, CESAREAN
SECTION, CAN BE SOMEWHAT
MITIGATED BY BREASTFEEDING, SO
DIFFERENCES AFTER C-SECTION IN
INFANT MICROBIOME ARE MINIMIZED
AND GO AWAY FASTER IN BABIES WHO
ARE BREASTFED AFTER CASAREAN
DELIVERY, SO BREAST MILK IS A
GREAT SORT OF NATURAL
INTERVENTION WE CAN RECOMMEND TO
MOMS WHO HAD A C-SECTION, AND SO
THOSE DATA ARE PUBLISHED.
NEW DATA NOW I FIND REALLY
EXCITING SIMILAR WITH
ANTIBIOTICS.
ANTIBIOTICS PERTURB THE
MICROBIOME AND CAN HAVE A LONG
TERM IMPACT BACKUP WE FIND IN
THE COHORT YES ANTIBIOTICS
PERTURB THE MICROBIOME,
PREDISPOSING THE BABY TO ASTHMA
AND ALLERGIES, BUT IF THE BABIES
ARE BREASTFED AT THE TIME THEY
RECEIVE ANTIBIOTICS WE DON'T SEE
THAT CASCADE OF EVENTS.
SO AGAIN IF A BABY NEEDS
ANTIBIOTICS, NUMBER ONE WOULD BE
DON'T USE THEM IF THEY ARE NOT
NECESSARY BECAUSE THEY ARE
PRESCRIBED INCORRECTLY.
IF THE BABY NEEDS TRY TO MAKE
SURE THE BABY IS STILL BREASTFED
OR IF THEY AREN'T, BREAST MILK
COULD BE PROVIDED ALONGSIDE
ANTIBIOTICS AS SUPPLEMENT TO
PREVENT COLLATERAL DAMAGE WE
SOMETIMES CALL IT ON THE
MICROBIOME.
>> THANK YOU.
WE NEED TO MOVE ON.
WE STILL HAVE LOTS OF QUESTIONS.
I GOT REALLY EXCITED, AS YOU CAN
TELL, AND MAYBE WE LINGERED TOO
LONG.
WE'LL MOVE TO THE NEXT
PRESENTATION.
I'LL INVITE MY CO-MODERATOR TO
INVITE THE NEXT SPEAKER.
>> THANK YOU, MEGAN.
WE'RE RECEIVING LOTS OF
QUESTIONS ONLINE.
WE REALLY APPRECIATE IT.
AND FOR THOSE WE CAN'T ANSWER IN
REAL TIME WE'RE CAPTURING THEM
AND WILL CERTAINLY TAKE THEM TO
HEART AND ADDRESS THEM
THROUGHOUT THIS ENDEAVOR AND
WORKSHOP.
I HAVE THE PRIVILEGE OF BRINGING
TO THE STAGE KIRSI.
TAKE IT AWAY.
>> CAN I HEAR ME?
OKAY, GREAT.
THANK YOU SO MUCH, FOR INVITING
ME TO TALK ABOUT INFANT IMMUNE
SYSTEM DEVELOPMENT.
I'M A CLINICAL IMMUNOLOGIST AND
ALLERGIST, MY PERSPECTIVE TODAY
IS GOING TO BE SHARING SOME OF
THE IMPORTANT KEY ASPECTS OF
IMMUNE SYSTEM DEVELOPMENT IN THE
MOSTLY FIRST YEAR OF LIFE.
AND THEN TRYING TO TAKE A LOOK
AT A PEEK INTO WHAT OTHER KIND
OF FACTORS THAT MAY IMPACT THAT
IMMUNE TRAJECTORY, ESPECIALLY AS
IT PERTAINS TO OR IS RELEVANT TO
BREAST AND FORMULA FEEDING.
>> CAN YOU SWITCH YOUR VIEW?
>> OKAY.
>> HOW ABOUT THIS?
>> PERFECT.
>> OKAY, GREAT.
HERE ARE MY DISCLOSURES, NONE
ARE REALLY RELEVANT TO WHAT I'M
TALKING ABOUT TODAY.
SO, INFANCY IS NATURALLY A
PERIOD OF RAPID IMMUNE SYSTEM
MATURATION, EXPOSURE TO NOVEL
ANTIGENS AND EXTRAUTERINE LIFE,
CHANGES IN POPULATIONS.
THIS GRAPH ILLUSTRATES
DEVELOPMENT OF MAJOR IMMUNE CELL
POPULATIONS IN THE BLOOD, ALL
THE WAY TO SIX MONTHS OF LIFE ON
THE RIGHT.
EACH ONE OF THESE COLUMNS
REPRESENTS AN INDIVIDUAL.
SO THERE ARE INDIVIDUALS ALL THE
WAY UP TO LIKE 200 DAYS OF LIFE
HERE ON THE RIGHT-HAND SIDE.
AND PLEASE NOTE THIS
ILLUSTRATION SHOWS THE FRACTION
OF CELLS AS TOTAL, DOESN'T
REFLECT THE CHANGES IN ABSOLUTE
COUNTS.
I'LL GET BACK TO THAT IN A
LITTLE BIT.
FOCUSING ON EARLY POST-NATAL
LIFE HERE, WE SEE THERE'S A
SPECIFIC COMPOSITION OF IMMUNE
CELLS, WITH NEUTROPHILS SHOWN
HERE IN VIOLET COLOR, OR PURPLE.
AND THEN CD4+ T CELLS IN LIGHT
GREEN -- LIGHT BLUE, AND
MONOCYTES IN YELLOW.
THOSE ARE THE MAIN POPULATIONS
GENERALLY IN EARLY LIFE, HOWEVER
AS THESE INFANTS AGE THERE'S A
SIGNIFICANT DECREASE IN THE
NUMBER OF NEUTROPHILS, FOR
EXAMPLE, AS WELL AS MONOCYTES TO
SOME EXTENT.
AND WITH THE SIMULTANEOUS
INCREASE IN THE NUMBER OF THESE
CD4+ T CELLS, CD4+ T CELLS IN
TEAL, AS WELL AS NK CELLS IN
ORANGE, AND B CELLS AS SHOWN IN
THIS LIGHT PURPLE COLOR HERE.
SO, THERE'S THIS RAPID CHANGE
THAT HAPPENS IN IMMUNE CELL
POPULATION.
IF WE FOCUS ON T CELLS, AS IN
THE PREVIOUS GRAPH IT SHOWED
THERE IS INCREASE IN PROPORTION
OF CD4 T CELLS, AND HERE NOW
THIS GRAPH IS ACTUALLY
INDICATING THAT ABSOLUTE
NUMBERS, SO SLIGHTLY DIFFERENT
REPRESENTATION.
COLLECTIVELY WE CAN CONDITION
INCLUDE -- CONCLUDE IN THE
FIRST YEAR OF LIFE, T CELLS IN
ABSOLUTE NUMBER FOLLOWED BY
DECREASE IN THE SECOND YEAR OF
LIFE OVER HERE.
AND CONTRASTING WITH CD8+ T
CELLS THERE'S A MODEST INCREASE
IN FIRST YEAR WITH SOME
DECONVOLUTION IN SECOND YEAR OF
LIFE.
HOWEVER, A MORE CAREFUL LOOK AT
THE TYPES REVEALS IT'S NOT
JUST -- IT'S REALLY ONLY THE
NUMBER OF NAIVE CELLS UP HERE
THAT ARE INCREASED IN THIS TIME
WHEREAS TERMINALLY
DIFFERENTIATED EFFECTOR MEMORY
AND CENTRAL MEMORY CELLS, SHOWN
HERE, ARE REALLY NOT IMPACTED IN
TERMS OF THEIR ABSOLUTE NUMBERS.
THE SAME APPLIES FOR CD8+ CELLS,
NAIVE POPULATION IS THE ONE THAT
INCREASES, IF ANYTHING.
THERE'S ALSO INCREASE IN
ABSOLUTE NUMBER OF T REGULATORY
CELLS, THESE ARE THE TRADITIONAL
CD4+, CD25+, CD27 NEGATIVE
CELLS, SIGNIFICANT INCREASE IN
FIRST YEAR WITH SOME DECREASE IN
THE SECONDS YEAR OF LIFE AND
THEN PLATEAU IN LATER CHILDHOOD
AND INTO ADULTHOOD.
HOWEVER, WHEN YOU LOOK -- THIS
IS ABSOLUTE NUMBERS.
HOWEVER, WHEN YOU LOOK AT THE
PROPORTION OF THESE T REGULATORY
CELLS, THE COMPOSITION OR NUMBER
OF CD4+ LYMPHOCYTES, RELATIVE
CONTRIBUTION REMAINS STABLE.
THIS INCREASE IN NUMBER OF T
REGULATORY CELLS WHICH BY THE
WAY ARE RESPONSIBLE FOR
REGULATING T CELL AND B CELL
RESPONSES, MIRRORING INCREASE
YOU SEE THIS INCREASE IN CD--
SORRY, CXCR 5-PLUS, CD4, BASED
ON IgA AND IgG PRODUCTION.
SO, THESE CELLS ARE NATURALLY
THE SOURCE OF THESE CR
IMMUNOGLOBULINS.
THIS IS A FAMOUS GRAPH LOOKING
AT THE PRODUCTION OF
IMMUNOGLOBULINS OVER THE
IMMEDIATE POST-NATAL LIFE, INTO
ADULTHOOD.
AND HERE REGARDING THE IgA AND
IgM, LET'S LOOK AT THOSE
FIRST, ONE IN GREEN AND BLUE.
RAPID INCREASE IN FIRST TWO
MONTHS OF LIFE WHICH WITH MORE
MODEST INCREASE THROUGH THE
FIRST YEAR OF LIFE HERE UNTIL
TWO YEARS OF LIFE AND THEN AGAIN
MUCH MORE RAPID INCREASE IN
IgA AND MORE MODEST INCREASE
IN IgM WHEREAS THE LEVELS
ULTIMATELY KEEP GOING UNTIL
REALLY EARLY ADULTHOOD AND DON'T
REALLY REACH THESE ADULT LEVELS
UNTIL MUCH LATER IN CHILDHOOD.
AS OPPOSED TO IMMUNOGLOBULINS IN
EARLY LIFE WE HAVE FIRST COUPLE
MONTHS YOU HAVE SIGNIFICANT
LEVELS OF SERUM IMMUNOGLOBULIN
G, WHICH IS OF MATERNAL ORIGIN,
REFLECTS TRANSFER OF
IMMUNOGLOBULIN, G, REFLECTED
WITH NADIR AROUND THREE, FOUR,
FIVE MONTHS OF AGE, AT THAT
POINT A CHILD'S PRODUCTION KICKS
OFF TO SIGNIFICANT LEVEL SO
THESE LEVELS START TO GO UP AND
REACH NICE LEVELS BY
MID-CHILDHOOD.
HAVE YOU PRODUCTION OF
ANTIBODIES AND VACCINE
RESPONSES.
IMMUNE CELL STIMULATION HAPPENS,
THE GUT.
JOE NEU REFLECTED ON THIS, IN
THE MUCOSA, ANTIGEN CAPTURE, FOR
EXAMPLE, IN THIS GUT
PRESENTATION HERE.
ANTIGENS ARE CAPTURED.
THEN PRESENTED TO BE T CELLS, B
CELLS, DENDRITIC CELLS,
DIFFERENTIATION OF CELLS
RESPONSIBLE FOR PRODUCING
IMMUNOGLOBULINS PUMPED ACTIVELY
INTO THE GUT LUMEN TO CAPTURE
SPECIFIC ANTIGENS OF INTEREST.
THIS IS REALLY THIS EARLY LIFE
WHEN ANTIBODY PRODUCTION IS.
THERE'S DEVELOPMENT OF
IMMUNOGLOBULINS SUCH AS IgE,
KNOWN FOR ASSOCIATION WITH
ATOPIC DISEASE.
THIS GRAPH HERE SHOWS INCREASE
IN IgE BETWEEN TWO AND TEN
YEARS OF LIFE IN THOSE
INDIVIDUALS WHO DO NOT DEVELOP
ALLERGIC MANIFESTATION.
MAYBE A MODEST INCREASE AS
COMPARED TO THOSE INDIVIDUALS
THAT ARE DEVELOPING WHEEZING
ILLNESS OR ALLERGIC RHINITIS, A
TREND OF DEVELOPMENT IN FIRST
HALF OF THE CHILDHOOD.
THIS COINCIDES WITH DEVELOPMENT
OF ATOPIC DISEASE, IN EARLY LIFE
IN THE FIRST COUPLE YEARS OF
LIFE ECZEMA SHOWN IN BLUE AS
WELL AS FOOD ALLERGIES IN RED,
PREVALENT, ATOPIC DISEASE IN
EARLY LIFE, WITH SIGNIFICANT
DECREASE AS FOOD ALLERGIES ARE
OUTGROWN WITH SIMULTANEOUS
INCREASE IN RESPIRATORY
ALLERGIES SUCH AS ASTHMA SHOWN
IN GREEN AND ALLERGIC RHINITIS
IN ORANGE.
HIGHLIGHTS OF MAIN FOODS
RESPONSIBLE IN EARLY LIFE ARE
EGG, MILK, PEANUT.
THESE INDIVIDUALS HAVE FAILED TO
DEVELOP TOLERANCE TO THESE
FOODS, WHICH IS THE MOST COMMON
DEFAULT RESPONSE OF THE IMMUNE
SYSTEM IN MOST OF US.
SO THESE INDIVIDUALS ARE
TYPICALLY AT GENETIC RISK AND
THEY HAVE BEEN EXPOSED TO FOOD
ANTIGENS BY ROUTES THAT ARE NOT
TOLERIZING WHICH IS THE CASE IN
ORAL EXPOSURE, BUT THEY MAY HAVE
HAD, FOR EXAMPLE, SKIN EXPOSURE
WHICH IS RATHER SENSITIZING.
AND THESE FOOD ALLERGIES CAN
OFTEN BE OUTGROWN INDICATED AS
TENDENCY TO VALUE NOT TOLERANCE
IN CHILDHOOD, AND THAT COINCIDES
WITH DEVELOPMENT OF T REGULATORY
CELLS AND DECREASE IN LYMPHOCYTE
PROLIFERATION.
AS WELL AS INCREASE IN IgG,
SPECIFICALLY IgG 4 ISOTYPE AND
DECREASE IN IgE SO NATURAL
EVENTS IN FOOD ALLERGY.
INTERESTINGLY IN EARLY LIE
THERE'S LIFE RAPID CATCH-UP CAN
HAPPEN.
THIS STUDY NOT PEER REVIEWED YET
SHOWS T CELL PHENOTYPE CONVERGES
WITHIN THE FIRST YEAR OF LIFE IN
PRE-TERM AND TERM INFANTS.
THEY SHOW THE MAP OF
PRESENTATION HERE THAT FULL TERM
AND PRE-TERM INFANTS AT BIRTH
ARE QUITE DIFFERENT FOR T CELL
PHENOTYPES, BUT THEY START TO
CONVERGE AND BY THE AGE OF 12
MONTHS THEY ARE LOOKING RATHER
SIMILAR.
THERE'S THIS CATCH-UP THAT
HAPPENS OVER TIME.
SO SIGNIFICANT LIFESTYLE FACTORS
THAT CAN IMPACT IMMUNE SYSTEM
DEVELOPMENT IN FIRST YEAR, OUR
RESEARCH PROGRAM LOOKED AT
FARMING LIFESTYLE, I'LL SHARE A
LITTLE BIT OF DATA THAT WAS
RECENTLY PUBLISHED.
THE MODEL POPULATION IS OLDER
MENNONNITES OF WESTERN NEW YORK,
LOW RATE OF ALL THESE ATOPIC
ALLERGIC DISEASES.
WHEN WE LOOKED AT GUT
MICROBIOME, AVERAGE OF TWO
MONTHS OF AGE, WE NOTED
BIFIDOBACTERIA ARE ENRICHED IN
OLDER MENNONNITES, AS OPPOSED TO
ROCHESTER, WE TOOK A CLOSER LOOK
AT THE TYPE OF STRAINS OF
BIFIDOBACTERIA PREVALENT IN
OLDER MENNONITE IN RED, HIGHLY
ENRICHED IN INFANTS BORN TO THE
MENNONITE COMMUNITY, LESS THAN
100 DAYS OR OVER 100 DAYS OLD,
BEGS THE QUESTION WHETHER SHE'S
GUT MICROBIOME STRAINS MIGHT BE
PLAYING A ROLE IN THE PROTECTION
AGAINST ATOPIC DISEASES THAT
HAPPENS IN THIS COMMUNITY.
SO THIS MICROBIOME AND INFANT
IMMUNE SYSTEM ACCESS COMES INTO
SCRUTINY, WE'RE FURTHER
EXPLORING IMMUNE SYSTEM
DEVELOPMENT IN THIS POPULATION.
I'M NOT SHARING THAT DATA
BECAUSE IT'S NOT PUBLISHED AT
THIS POINT.
THE OTHER ASPECTS THAT IMPACT
IN EARLY LIFE OBVIOUSLY INCLUDE
HUMAN MILK COMPONENTS, JUST
LISTING A FEW, SOME OF THOSE
THAT I'M PARTICULARLY FOND OF
ARE THE ANTIGENS, FOOD ANTIGENS
IN BREAST MILK, IgA,
CYTOKINES, MICROBIOME, AS WELL
AS OLIGOSACCHARIDES.
I WON'T GO IN DETAIL ABOUT THESE
COMPONENTS BUT THEY CAN IMPACT
IN MULTIPLE WAYS, PROVIDE
ANTIGENS, MUCOSAL BARRIER,
IMMUNE MICROENVIRONMENT IN TERMS
OF CYTOKINE MILIEU, THEY CAN
PROVIDE MICROBIOME FEEDING OR
SEATING INTESTINAL MICROBIOME
AND PROVIDING INITIAL ANTIGEN
AND EPITOPE REPERTOIRE.
HERE SHOWING STUDIES WE HAVE
LOOKED INTO DIFFERENT
COMPONENTS, MIGHT RELATE TO
ALLERGIC OUTCOMES IN INFANTS,
AND QUICKLY JUST SHARING THE
DATA HERE THAT WE LOOKED AT COW
MILK ALLERGY AS OUTCOME IN A
POPULATION, WHEREAS NO ALLERGY
AND WE SHOW SPECIFIC LEVELS
UPREGULATED IN MOTHERS MILK WHEN
INFANTS DID NOT DEVELOP MILK
ALLERGIC OUTCOMES AND
OLIGOSACCHARIDE IN HIGHER LEVELS
IN THOSE PRESENTED AGAINST
ATOPIC DISEASES.
HUMAN MILK IgA IS ONE OF THE
MOST IMPORTANT IMMUNOGLOBULINS
IN BREAST MILK, PRODUCED IN
LARGE QUANTITIES DAILY WITH
LEVELS DECREASING OVER TIME IN
BREAST MILK AND SPECIFICITY
REFLECTS INTRAMAMMARY LINK, IN
OTHER WORDS, SPECIFICITY OF FOOD
AND ENVIRONMENTAL AS WELL AS
BACTERIAL, VIRAL COMPOSITION
THAT THE MATERNAL GUT AND OTHER
MUCOSAL TRACTS HAVE BEEN
ENCOUNTERED.
SO BECAUSE THE QUESTION WAS TO
REALLY ALSO COMMENT ON THE
CLINICAL OUTCOMES THAT I WOULD
FIND OF INTEREST IN TERMS OF
IMMUNE SYSTEM DEVELOPMENT AND
LISTING THOSE HERE FOR YOUR
PERUSAL.
REALLY PROTECTION AGAINST
INFECTIONS IS VERY IMPORTANT IN
FIRST YEAR OF LIFE.
YOU CAN SEE MULTIPLE INFECTIONS,
ORAL TOLERANCE DEVELOPMENT OR
FAILURE TO DEVELOP TOLERANCE
THAT LAPS IN FOOD ALLERGY,
CELIAC DISEASE, EVEN EARLY
INFLAMMATORY BOWEL DISEASE AS
WELL AS YOU CAN HAVE OTHER
CHRONIC INFLAMMATORY CONDITIONS,
SUCH AS ALLERGIC DISEASES I JUST
MENTIONED, ECZEMA, ASTHMA,
ALLERGIC RHINITIS, AUTOIMMUNE
DISEASE SUCH AS DIABETES TYPE 1
AND SO FORTH.
SOME MARKERS MENTIONED HERE I
FEEL THAT MIGHT BE CAPTURING
IMMUNE SYSTEM DEVELOPMENT IN
EARLY LIFE BLOOD COUNTS,
DIFFERENT T- AND B-CELL
POPULATION, LYMPHOCYTE
RESPONSES, MAYBE LOOKING INTO
SPECIFIC BIOACTIVES AT DIFFERENT
TIME POINTS IN THE FIRST YEAR OF
LIFE.
OBVIOUSLY THAT DEPENDS ON WHAT
THE QUESTION IS TO BE ANSWERED.
SO WITH THAT I WANTED TO THANK
YOU FOR ATTENTION AND OPEN FOR
QUESTIONS.
>> LOTS OF QUESTIONS ARE COMING
IN.
I'LL START AND ON AN EARLIER
SLIDE YOU SHOWED DATA THAT
INDICATE IT'S CHANGE BETWEEN THE
FIRST WEEK OF LIFE AND 9 TO 15
MONTHS, DIVERGENCE AND SHIFT
THEREAFTER.
IS THAT DATA ABOUT THE CD CELL
POPULATIONS IN THE FIRST YEAR OF
LIFE?
>> THERE ARE SOME DATA, FOR THE
SAKE OF TIME I DID NOT PUT
EVERYTHING HERE.
DATA IS QUITE LIMITED BECAUSE TO
FIND SOLELY FORMULA-FED INFANTS
IS CHALLENGING, SO A LOT OF
INFANTS TEND TO GET A LITTLE BIT
OF BREAST MILK IN THE FIRST FEW
YEARS OF LIFE AT LEAST, A
CRITICAL PERIOD, TO HAVE SOLELY
BREASTFED AND SOLELY FORMULA FED
INFANTS I THINK THAT'S
CHALLENGING.
DATA HAVE INDICATED SHIFTS FROM
THESE T CELL POPULATIONS IN
FACT.
>> AND THE IgE DIDN'T DIDN'T
INCLUDE A LOT OF DATA BEFORE 24
MONTHS OF LIFE.
IS THERE KNOWN DIFFERENCE IN
IgE STATUS OF BREASTFED
INSTANTS VERSUS THOSE FED
FORMULA IN THE FIRST YEAR OF
LIFE?
>> I DON'T THINK IgE STATUS
HAS BEEN SPECIFICALLY LOOKED AT
BUT AS MANY OF YOU KNOW THERE
ARE MULTIPLE STUDIES THAT HAVE
LOOKED INTO WHETHER
BREASTFEEDING, WHEEZING ILLNESS,
AND DATA IS A LITTLE BIT ALL
OVER THE PLACE BUT CONSENSUS BY
NOW THAT HAS BEEN CAPTURED IN
SYSTEMATIC META-ANALYSIS IS
BREASTFEEDING, EXCLUSIVELY, AS
WELL AS BREASTFEEDING GENERALLY
IS SHOWN TO BE PROTECTIVE
AGAINST DEVELOPMENT OF TRANSIT
WHEEZE, WHEEZING AT FIVE YEARS
OF AGE AS WELL AS ATOPIC
DISEASE.
THERE ARE NO GREAT DATA FOR FOOD
ALLERGY AND IT HAS TO DO WITH
THE DIAGNOSTIC MODALITIES THAT
WE NEED TO HAVE IN PLACE FOR
FOOD ALLERGY, CAPTURE OF FOOD
ALLERGY, YOU HAVE TO DO CLINICAL
WORK.
UNFORTUNATELY THE STUDIES UP TO
DATE HAVEN'T REALLY BEEN POWERED
WITH METHODOLOGIES NOT INCLUDING
FOOD ALLERGY AS OUTCOME SO IT'S
UP IN THE AIR BUT THERE SEEMS TO
BE SOME PROTECTION AGAINST AT
LEAST SOME ATOPIC DISEASES BY
BREASTFEEDING.
PARTICULARLY LONGER
BREASTFEEDING PERIODS.
GOOD QUESTION.
>> THE NEXT QUESTION, VERY
PRACTICAL.
HAVE THERE BEEN THOUGHTS ABOUT
ADDING PROTEINS THAT MIGHT
SENSITIZE AN INDIVIDUAL OR MIGHT
CAUSE DIFFERENT ALLERGY, ADDING
THAT TO INFANT FORMULA WITH
GOALS OF PREVENTION?
>> YEAH, THAT'S EXACTLY WHY I
INCLUDED MY LAST SLIDE
ASSESSMENT OF SPECIFIC
ANTIBODIES, FOR EXAMPLE.
THERE'S A PUSH FOR EARLY
INTRODUCTION OF PEANUT PROTEIN,
FOR EXAMPLE, AT FOUR MONTHS OF
AGE APPROXIMATELY, TO SOME
EXTENT FOR EGG SHOWN TO BE
HIGHLY PROTECTIVE AGAINST
DEVELOPMENT OF FOOD ALLERGY,
PEANUT ALLERGY, PERHAPS EGG
ALLERGY AS WELL.
THERE MIGHT BE INTEREST IN
ADDING SOME HIGHLY ALLERGENIC
FOOD PROTEINS IN INFANT FORMULAS
AND I THINK SPECIFICALLY LOOKING
AT ANTIBODY RESPONSES AS WELL AS
FOOD ALLERGY BECOMES VERY
IMPORTANT FOR THOSE SETUPS.
>> WITH THE EVIDENCE WE SHOULD
BE LOOKING AT THE BRAIN I WANTED
TO SPEND TIME CONSIDERING HOW WE
MIGHT ASSESS NUTRIENT EFFECTS ON
THE DEVELOPING NEUROLOGIC
SYSTEMS SPECIFICALLY IN INFANTS.
FIRST A FEW WORDS ABOUT STUDY
DESIGN.
THIS IS REALLY DRAWING ON MY HAT
AS EPIDEMIOLOGIST, WE NEED TO
THINK HOW WE APPLIED RIGOR HERE.
THE BEST DESIGN IS GOING TO BE
RANDOMIZED CONTROLLED TRIAL
COMPARING WITH AND WITHOUT,
SINGLY OR IN COMBINATION,
INCLUDING BREASTFED REFERENCE
REPRESENTS GROUP BUT WE DO NEED
TO RECOGNIZE AND I WANT TO
EMPHASIZE WHILE WE OFTEN SEE
DIFFERENCES BETWEEN FORMULA FED
AND BREASTFED INFANTS, STUDIES
ARE NOT WELL DESIGNED TO
MINIMIZE CONFOUNDING.
IN MY EXPERIENCE THESE
DIFFERENCES ARE HIGHLIGHTED IN A
WAY CONFUSING OR EVEN
MISLEADING.
RELEVANT COMPARISON IS BETWEEN
INFANTS WITH STANDARD FORMULA
AND BIOADDITIVES.
IN TERMS OF OUTCOME ASSESSED AT
THE END OF INTERVENTION OR
BETTER WITH REPEATED MEASURES
OVER THE COURSE OF INTERVENTION,
TRIALS POWERED TO DETECT
MEANINGFUL DIFFERENCE ALSO ONE
THAT IS PLAUSIBLE.
AND TAKE EXPECTED ATTRITION IN
ACCOUNT.
THOSE OF US WHO WORK IN THE
FIELD ASPIRE TO FINE BENEFITS.
WHEN WE NEW THINK ABOUT MAKES
IT'S HELPFUL TO REVIEW CONCEPT
OF BIOINDICATOR, WE'RE LOOKING
FOR BIOINDICATORS THAT TELL US
ABOUT FUNCTIONAL RESPONSE TO
INTERVENTION.
THAT EFFECT OF SEVERAL FACTORS
OPERATING WITHIN COMPLEX
BIOLOGIC SYSTEM.
IN TERMS OF SELECTING MEASURES
IT'S HELPFUL TO REVIEW KEY
CONCEPTS ABOUT NUTRIENT EFFECT
ON BRAIN DEVELOPMENT.
AND WE SHOULD REALIZE THE SAME
CONCEPTS APPLY TO OTHER EARLY
LIFE EXPOSURES ON THE BRAIN SUCH
AS ENVIRONMENTAL TOXINS LIKE
LEAD AND SOCIAL INTERACTIONS
NURTURING DEVELOPMENTAL
STIMULATION ALONGSIDE FEEDING
AND OTHER SETTINGS.
FIRST IT IS MOST RAPIDLY
DEVELOPING REGION OF PROCESSES
MOST VULNERABLE, AND WE CAN
PREDICT FUNCTIONS MAPPING TO
THOSE REGIONS AND PROCESSES WILL
BE AFFECTED.
A RELATED POINT IS THAT THE SAME
EXPOSURE MAY HAVE DIFFERENT
AFFECTS DEPENDING ON TIMING, SO,
FOR EXAMPLE, A PRENATAL EXPOSURE
MAY BENEFIT BLOOD DAMAGE,
HIPPOCAMPUS, SAME EXPOSURE
P OSTNATALLY MIGHT AFFECT
PREFRONTAL CORTEX AND
CONNECTIONS WITH OTHER PARTS OF
THE BRAIN.
UNDERSTANDING THIS MIGHT LEAD TO
EVALUATE EFFECT ON MEMORY OR
EXECUTIVE FUNCTION.
AND AS SHOWN IN THIS FIGURE,
WITH TIME ON THE Y-AXIS,
DIFFERENT AREAS OF THE BRAIN
MYELINATE AT DIFFERENT TIMES
MEASURES GROUNDED IN
UNDERSTANDING OF TIMING, IN THE
CASE OF FORMULA WE SHOULD BE
LOOKING AT DEVELOPMENTAL EVENTS
IN THE FIRST SIX MONTHS WHEN
FORMULA IS SOLE DIET.
IT'S IMPORTANT TO RECOGNIZE
INHERENT CHALLENGES IN ASSESSING
EFFECT OF EARLY NUTRITION ON
NEUROLOGIC SYSTEM.
FIRST YOUNG INFANTS HAVE A
LIMITED REPERTOIRE OF BEHAVIORS
AND AS I WILL DISCUSS IN A
MOMENT THERE'S INNOVATIVE
PHYSIOLOGY-BASED WAYS TO TAP
INTO INFANT BRAIN FUNCTION,
WHETHER DEFECTED IN THIS WAY
PREDICTING MEANINGFUL LONGER
TERM EFFECTS IS UNCLEAR.
COHORTS PROVIDE MORE
OPPORTUNITIES TO DETECT
MEANINGFUL DIFFERENCES
PARTICULARLY WITH RESPECT TO
COGNITIVE FUNCTION BUT RETENTION
OF COHORTS IS EXPENSIVE AND
CHALLENGING.
FINALLY THERE ARE TRADEOFFS,
SOME TOOLS REQUIRE SOPHISTICATED
EQUIPMENT AND HIGHLY TRAINED
PERSONNEL, HARD TO DEPLOY OVER
A ALARM COHORT.
IN YOUNG INFANTS MANY OF THESE
CENTER ON MOTOR SYSTEM,
TRADITIONAL ASSESSMENT TOOLS TO
EVALUATE MUSCLE TONE AND REFLEX
AND INTEREST IN QUALITY OF
SPONTANEOUS MOVEMENTS AS SHOWN
IN IMAGES HERE.
IN TERMS OF COGNITION IN YOUNGER
INFANTS IT IS POSSIBLE TO MAKE
INFERENCES ABOUT MEMORY AND
LEARNING THROUGH EXAMINING
VISUAL ATTENTION TO NOVEL AND
FAMILIAR STIMULI, TASKS WHICH
REQUIRE INTACT VISUAL SAYS ITEM,
USED SUCCESSFULLY IN STUDIES,
FOR EXAMPLE, OF SUPPLEMENTATION.
SCALES NOT USEFUL UNTIL AT LEAST
A YEAR OF AGE EVALUATE NOT JUST
MOTOR AND COGNITIVE FUNCTION BUT
ALSO LANGUAGE AND SOCIAL
DOMAINS.
THERE ARE ALSO MORE HIGH TECH
APPROACHES TO EVALUATING INFANT
BRAIN FUNCTION AND STRUCTURE.
FIRST EEG-BASED APPROACHES WHERE
WE PROVIDE VISUAL OR AUDITORY
STIMULUS AND MEASURE RESPONSE TO
THE STIMULUS.
AGAIN IT'S POSSIBLE TO MAKE
INFERENCES ABOUT MEMORY AND
LEARNING BY COMPARING RESPONSES
TO NOVEL AND FAMILIAR STIMULI.
ALSO, PROCESSING SPEED IS
THOUGHT TO INDEX MYELINATION
WITH FASTER PROCESSING
INDICATING GREATER MYELINATION.
IN VERY YOUNG INSTANTS RESTING
EEG PATTERNS CAN PROVIDE AN
INDEX.
BRAIN STRUCTURE, AS NOTED IN OUR
PREVIOUS WORK, MRI CAN BE
USEFUL, FOR EXAMPLE, MRI STUDIES
IN PRE-TERM AND FULL-TERM
INFANTS DEMONSTRATED DIFFERENCES
IN STRUCTURE BETWEEN BREASTFED
AND FORMULA-FED INFANTS AND
DIFFUSION TENSOR IMAGING DTI CAN
DEMONSTRATE DIFFERENCE IN
MYELINATION.
AS NOTED, MRI SUCCESSFULLY IN
PRE-TERM NEWBORNS BUT KEEPING A
BABY STILL WITHOUT SEDATION CAN
BE CHALLENGING AND IS REALLY
INTERESTING AND IMPORTANT TO
NOTE THAT MOVEMENT CAN BE NOT
JUST INTRODUCING DATA BUT ALSO
BIAS.
PARTICIPANT REPORTED MEASURES
ARE SAYS.
SUCH AS THE QUESTIONNAIRE,
CAPTURING PARENT CONCERNS ABOUT
DEVELOPMENT CAN ALSO BE USEFUL
WITH INFANT TODDLER QUALITY OF
LIFE QUESTIONNAIRE, AND PARENT
REPORT OF BEHAVIOR CAN BE
ASSESSED WITH TOOLS SUCH AS BABY
PEDIATRIC SYMPTOM CHECK LIST.
QUESTIONNAIRE BASED ASSESSMENTS
ARE MORE SCALABLE THAN MEASURES
IN THE PREVIOUS SLIDES BUT IT'S
UNCLEAR HOW SENSITIVE THIS
APPROACH MAY BE AND IT DEPENDS
ON ACCURACY OF PARENT REPORT
WHICH ITSELF DEPENDS ON MATERNAL
FACTORS.
I WON'T SPEND TIME TALKING ABOUT
MEASURES IN OLDER CHILDREN BUT
WANT TO MENTION NIH TOOLBOX
DEVELOPED WITH VALIDITY AND
SCALABILITY IN MIND, AND EARLY
CHILDHOOD COGNITION BATTERY
APPROPRIATE FOR CHILDREN 3 TO 6
YEARS TO ASSESS ATTENTION AND
EXECUTIVE FUNCTION MEMORY AND
LANGUAGE.
NOW I'D LIKE TO WALK THROUGH A
RECENTLY PUBLISHED STUDY
ILLUSTRATING SOME CONCEPTS AND
TOOLS I'VE BEEN DISCUSSING.
COGNIS STUDY FROM SPAIN,
SUPPLEMENTED WITH BIOACTIVES ON
THE SLIDE.
MANY HAVE AT LEAST PLAUSIBLE
EFFECTS ON BRAIN DEVELOPMENT.
THERE WAS A CONTROL GROUP
RANDOMIZED TO STANDARD FORMULA
AND REFERENCE GROUP OF BREASTFED
INFANTS, THIS TRIAL IS
SPECIFICALLY POWERED TO DETECT
HALF STANDARD DEVIATION
DIFFERENCE.
IN TERMS OF OUTCOMES AND RESULTS
THEY LOOKED AT GENERAL
MOVEMENTS, TWO, THREE, FOUR
MONTHS, DID NOT FIND ANY
DIFFERENCES.
IN TERMS OF VEPs, DIFFERENCE
IN FORMULA GROUPS AND BREASTFED
CONTROLS FAVORING BREASTFED
INFANTS, FEW DIFFERENCES BETWEEN
THE TWO FORMULA GROUPS.
SO HOW DO WE INTERPRET THESE
RESULTS?
IT IS POSSIBLE THAT THERE IS
TRULY NO EFFECT OF THIS
EXPERIMENTAL FORMULA ON ANY PART
OF THE INFANT BRAIN.
THAT IS A TRUE NEGATIVE.
IT'S ALSO POSSIBLE TO EXAMINE
CIRCUITS IN THE MOTOR AND VISUAL
SYSTEMS NOT AFFECTED WHILE
MISSING OTHERS OR THESE MEASURES
WERE NOT SUFFICIENTLY SENSITIVE
OR SAMPLE SIZE WAS JUST NOT
LARGE ENOUGH TO PICK UP SMALLER
BUT POTENTIALLY IMPORTANT
DIFFERENCES.
STILL A LOT TO LEARN HERE
CLEARLY.
FORTUNATELY, THIS STUDY ALSO
FOLLOWED CHILDREN TO TODDLER AGE
AND ASSESSED BEHAVIOR USING THE
CHECKLIST.
THEY FOUND BETTER OUTCOMES IN
EXPERIMENTAL AS COMPARED WITH
STANDARD FORMULA GROUP, FOR
EXAMPLE 81% CLASSIFIED AS NORMAL
FOR INTERNALIZING PROBLEMS IN
EXPERIMENTAL GROUP AS COMPARED
WITH 59% IN STANDARD FORMULA
GROUP.
EXPERIMENTAL FORMULA GROUP
SHOWED HIGHER RATE OF NORMAL FOR
EFFECTIVE PROBLEMS THAN THE
STANDARD GROUP.
AND IN ANOTHER ASSESSMENT AT
PRESCHOOL AGE 4 YEARS IDENTIFIED
IMPROVED LANGUAGE FUNCTION IN
THE EXPERIMENTAL FORMULA
CHILDREN.
FIRST, ASSESSMENT IN INFANCY
EVEN SOPHISTICATED ONES MAY MISS
EFFECT OF INTERVENTION.
WE NEED TO KEEP INNOVATING
DEVELOPING TOOLS AND EVALUATING
WIDE RANGE OF INFANTS NEUROLOGIC
FUNCTION IN A WAY FEASIBLE AND
SCALABLE AND CAN APPRECIATE
CRITICAL IMPORTANCE OF FOLLOWING
STUDY COHORTS INTO CHILDHOOD.
TO WRAP UP LET'S HONE IN ON KEY
CONCEPTS AROUND IDEAL
MEASUREMENT ON INFANT NEUROLOGIC
OUTCOME, DRAWING ON WHAT WE KNOW
ABOUT INFANT BRAIN DEVELOPMENT.
FIRST, HIGH LEVEL, LOOKING FOR
PHYSIOLOGICALLY SIGNIFICANT
BIOINDICATORS.
MEASURES THAT INDICATE NET
EFFECT OR RESPONSES IN A COMPLEX
BIOLOGICAL SYSTEM, THE BRAIN.
AND THE UNDERLYING DEVELOPMENTAL
PROCESSES AND TIMING
SPECIFICALLY KEY PROCESSES OF
MYELINATION AND BUILDING AND
REFINING OF CONNECTIONS BETWEEN
NEURONS AND BRAIN REGIONS IN THE
FIRST POST-NATAL YEAR, POINT US
TO FUNCTION THAT CAN BE
DISRUPTED OR ENHANCED IN THE
CONTEXT OF FORMULA AND
BIOACTIVES.
WE NEED TO APPLY HIGH LEVEL OF
RIGOR BOTH TO DESIGN OF STUDY
AND INTERPRETATION OF RESULTS.
IN TERMS OF MEASURES,
PHYSIOLOGICALLY RELEVANT
APPROACHES TO MEASURING
NEUROLOGIC FUNCTION IN INFANCY,
AND THESE CAN BE LEVERAGES BUT
ALSO HAVE LIMITATIONS.
LONGER FOLLOW-UP OF COHORTS IS
REALLY IMPORTANT USING RANGE OF
MEASURES THAT INCLUDE
PARENT-REPORTED INSTRUMENTS AS
WELL AS RESOURCES SUCH AS NIH
TOOLBOX WHICH ADDRESS THESE
ABILITY CHALLENGES AND TAP INTO
DOMAINS OF COGNITION AND
BEHAVIOR, IMPORTANT FOR LONG
TERM FUNCTIONING.
AND WITH THAT I AM HAPPY TO TAKE
QUESTIONS.
THANK YOU SO MUCH.
>> WONDERFUL.
THANK YOU SO MUCH, MANDY.
BEFORE I TURN THE FLOOR OVER TO
APRIL FOR THOSE WATCHING THE
VIDEOCAST I WANT TO APOLOGIZE.
WE WERE NOTIFIED THAT THERE WAS
SOME GLITCHES.
WE DO APOLOGIZE BUT I WANT TO
REASSURE YOU EVERYTHING IS BEING
CAPTURED AND WILL BE AVAILABLE
ONLINE IN ABOUT A WEEK TO TWO
WEEKS.
THOSE LINKS TO THE VIDEOCAST
THAT YOU TUNE INTO TODAY WILL
TAKE YOU TO THOSE RECORDINGS.
AGAIN, I DO APOLOGIZE FOR THE
TECHNICAL ISSUE.
THANK YOU FOR NOTIFYING US AS
QUICKLY AS IT HAPPENED.
I'LL TURN IT OVER TO APRIL.
>> THANKS, DREW.
AND AGAIN APOLOGIES TO OUR
AUDIENCE.
HOPEFULLY YOU WILL GET ACCESS TO
THE RECORDING SHORTLY AFTER
PUBLICATION.
SO DR. BELFORT, I HAVE A
QUESTION ABOUT HOW WE CAN BETTER
UNDERSTAND EFFECT OF NUTRIENT
COMPOSITION ON BRAIN GROWTH.
ESPECIALLY HOW IT CAN TRANSLATE
WHAT IS STUDIED IN ANIMALS
TOWARDS HUMANS.
THIS IS ALWAYS THE MILLION
DOLLAR QUESTION FOR REGULATORS.
I'M THINKING PARTICULARLY ABOUT
ACQUISITION OF LEARNING AND
MEMORY, RIGHT?
WHAT ABOUT SPATIAL MEMORY?
WE KNOW WE CAN MEASURE SPATIAL
MEMORY ACQUISITION THROUGH
VISUAL CUES IN RODENT MODELS IN
EARLY LIFE, CAN THIS INFORMATION
BE USED TO UNDERSTAND
ACQUISITION OF LEARNING AND
MEMORY PROCESSES OR AT LEAST
SPATIAL MEMORY IN INFANTS AS
THEY DEVELOP AND CAN WE LEARN
IMPACT EVER NUTRIENT CHANGES ON
MEMORY USING THE ANIMAL MODELS?
>> YEAH, THERE ARE A NUMBER OF
QUESTIONS PACKED IN THERE.
THIS IDEA OF STUDYING EFFECT OF
BIOACTIVE ADDITIV TO FORMULA IS
A PARADIGM.
WE RELY ON STUDIES, CAN'T
RANDOMLY ASSIGN A MOTHER TO
BREASTFEEDS OR FORMULA FEED.
THERE ARE WAYS TO APPROVE
ABILITY TO MAKE INFERENCES BUT
ULTIMATELY THERE WILL BE ALWAYS
THE CHALLENGE OF END MEASURED
CONFOUNDING.
IN THE PARADIGM OF ADDING
BIOACTIVES TO FORMULA AND
EXPLICITLY STUDYING EFFECT ON
DEVELOPING NEUROLOGIC SYSTEM,
THAT'S REALLY INCREDIBLE
OPPORTUNITY.
IN TERMS OF TRANSLATING FINDINGS
FROM ANIMALS TO HUMANS, I THINK
THIS TIMING ISSUE IS IMPORTANT.
ALIGNING THE TIMING OF
DEVELOPMENTAL EVENTS OF THE
PARTICULAR ANIMAL MODEL WITH
WHAT WE KNOW ABOUT NORMAL
DEVELOPMENT IN HUMAN INFANTS IS
REALLY IMPORTANT.
DESIGNING OUTCOME MEASURES THAT
TAP INTO THE SAME FUNCTION OR
STRUCTURES THAT ARE BEING SEEN
IN ANIMAL MODELS IS FEASIBLE.
EVEN IF WE DO FIND DIFFERENCES
IN SOME OF THESE, FOR EXAMPLE,
PHYSIOLOGY-BASED OR EVEN
BEHAVIORAL MEASURES IN INFANTS,
IT'S NOT TO SAY THOSE EFFECTS
WILL BE PERMANENT.
IN THEORY WE BELIEVE AND WE SEE
IN ANIMAL MODELS AND IN OTHER
SCENARIOS THAT THERE ARE
LONG-TERM EFFECTS BUT WE DON'T
ALWAYS SEE A CORRELATION BETWEEN
THESE INFANCY MEASURES AND
LONGER-TERM MORE FUNCTIONALLY
RELEVANT MEASURES.
I REALLY DO THINK AT THIS POINT
WHERE THE SCIENCE IS, YES, WE
HAVE SOME REALLY COOL WAYS TO
ASSESS INFANT NEUROLOGIC
FUNCTION.
SOMETIMES THOSE PREDICT LATER
MORE FUNCTIONALLY IMPORTANT
OUTCOMES, BUT NOT ALWAYS.
AND THERE'S STILL A LOT TO KNOW.
SO I THINK COMBINING INFANT
MEASURES WITH LONGER TERM
OUTCOMES IS REALLY IMPORTANT.
>> YEAH, THE WHOLE PHENOMENON OF
BRAIN PLASTICITY MAKES IT
DIFFICULT, RIGHT?
UNDERSTANDING THRESHOLDS THAT
HAVE NOT BEEN WELL DEFINED AND
WHAT CAN BE COMPENSATED THROUGH
PLASTIC MECHANISMS IN THE BRAIN.
ONE MORE QUESTION FROM MANDY AND
WE'LL MOVE TO THE PANEL
DISCUSSION.
SO DR. BELFORT, YOU SHOWED
NEUROLOGICAL BENEFITS FOR BREAST
MILK IN NICU, WAS THIS BASED ON
DONOR BREAST MILK AND IS THERE A
DIFFERENCE OR HAS IT BEEN
STUDIED IF'S IF THERE'S A
DIFFERENCE BETWEEN MOTHER'S MILK
AND DONOR MILK.
>> THIS HAS INVOLVED MATERNAL
MILK ONLY.
I WOULD SAY THE BEST STUDY OF
DONOR MILK AND NEURODEVELOPMENT
WAS CONDUCTED BY DEBBIE
O'CONNOR IN TORONTO, INFANTS
ALSO FED THEIR OWN MOTHER'S MILK
AND DID NOT FIND ANY
NEURODEVELOPMENTAL DIFFERENCES
AT 18 MONTHS AND I BELIEVE THEY
HAVE THE COHORT FOR LONGER
PERIOD OF TIME.
YOU CAN ASSIGN BABIES BUT CAN'T
RANDOMLY ASSIGN THEM TO RECEIVE
THEIR OWN MOTHER'S MILK BUT
GENERALLY THE STUDIES FAVOR
NEURODEVELOPMENTAL BENEFITS OF
MATERNAL MILK BUT NOT SO MUCH
DONOR MILK AT THIS POINT.
THANKS SO MUCH.
I WOULD LIKE TO INVITE PANELISTS
BACK ON STAGE TO TAKE GENERAL
QUESTIONS.
THAT MAY BE APPLICABLE ACROSS
THE PRESENTATIONS. THIS
HEARKENS BACK TO -- I'M SORRY,
I'M RUSHING AHEAD.
LET'S WAIT FOR THE SPEAKERS TO
GATHER.
I'D BE INTERESTED TO HEAR
PERSPECTIVES OF OTHER SPEAKERS.
WE MENTIONED SOME CONDITIONS
SUCH AS COLIC OR REFLUX THAT ARE
RELATIVELY COMMON AND CAN OCCUR
IF THEY ARE BREASTFED OR FORMULA
FED, YET WE DO SEE INTERVENTIONS
THROUGH FORMULA FEEDING TO
ADDRESS THESE, CURIOUS WHETHER
OR NOT BIOACTIVES AIMED TOWARDS
THESE CONDITIONS ARE ADDRESSING
SOMETHING THAT MIGHT BE A NORMAL
ASPECT OF THAT INFANT'S
DEVELOPMENT OR NEEDS TO BE
ADDRESSED AND HOW YOU CAN TELL
BETWEEN THE TWO, WONDERING IF
THEY ARE TRYING TO SOLVE A
PROBLEM THAT MIGHT NOT BE A
PROBLEM BUT MIGHT BE NORMAL
DEVELOPMENTAL PHENOMENON.
>> WELL, CERTAINLY
GASTROESOPHAGEAL REFLUX BY
ITSELF IS A CONDITION, NOT A
DISEASE.
GASTROESOPHAGEAL REFLUX DISEASE
IS SOMETHING THAT IS A DIFFERENT
ENTITY WHERE IT CAUSES
SIGNIFICANT ILLNESS IN THE CHILD
BUT THE GASTROESOPHAGEAL REFLUX
IS A NUISANCE BUT A BIG NUISANCE
FOR PARENTS AND BABIES.
THERE'S A LOT OF RESOURCES,
PLACED INTO DIAGNOSTICS FOR
THOSE KIDS, AND CAN CAUSE JUST A
TREMENDOUS AMOUNT OF ANXIETY
AMONGST THE FAMILIES OF KIDS
WITH GASTROESOPHAGEAL REFLUX.
SAME THING HOLDS WITH COLIC.
IN TERMS OF GASTROESOPHAGEAL
REFLUX, I THINK SOME OF THE
FORMULA COMPANIES HAVE TRIED TO
ADDRESS THAT BY USING THICKENED
FORMULAS, BY USING SPECIALIZED
FORMULAS THAT CONTAIN SOME
CEREAL BASES, DIFFERENT
CARBOHYDRATES, THOSE ARE
ACTUALLY IN SOME CASES CAUSING
PROBLEMS, LONGER-TERM PROBLEMS,
FOR COLIC I THINK THAT THIS IS
SOMETHING THAT SOME THE
COMPANIES HAVE BEEN TRYING TO
ADDRESS USING PROBIOTIC,
PRE-BIOTIC KINDS OF
TECHNOLOGIES, THE STUDIES I
THINK ARE STILL ONGOING WITH
MANY OF THOSE, AND I DON'T KNOW
IF LARS OR SOMEBODY ELSE IS
GOING TO ADDRESS THAT MORE IN
THE FUTURE.
>> WELL, MAYBE I COULD ADD AS AN
ALLERGIST I SEE A LOT OF THESE
CHILDREN WITH GASTROESOPHAGEAL
REFLUX OR REFLUX DISEASE, AS JOE
MENTIONED THIS IS, YOU KNOW, IT
DEPENDS WHAT THE SEVERITY OF THE
SYMPTOMS ARE WHETHER THAT'S
SOMETHING THAT NEEDS TO BE
ADDRESSED OR NOT.
THERE ARE CHILDREN WHO -- OR
BABIES WHO HAVE BEEN ABLE TO
THRIVE UP TO, YOU KNOW, THEY
HAVE REFLUX DISEASE UP TO THAT
POINT OR LIKE JOE SAID, THERE IS
QUITE A BIT -- WHEN BABY IS NOT
SLEEPING OVERNIGHT, PARENTS ARE
UP, IN THOSE EXTREME SITUATIONS
WE OBVIOUSLY DO ADDRESS THIS,
BUT I DON'T HAVE ANY SPECIFIC
THOUGHTS INTO THE FORMULA VERSUS
BREASTFEEDING, MOST OF THE
CHILDREN THAT I HAVE TO TAKE
CARE OF IN THESE SITUATIONS, IF
SYMPTOMS ARE SIGNIFICANT ENOUGH,
MAY END UP ON MEDICATION TRIALS
AND/OR ELIMINATION OF MILK
PROTEIN IN THEIR DIET WHICH IS
ACTUALLY RECOMMENDED BY THE
GUIDELINES AS A TRIAL SO IN
OTHER WORDS IF MOM IS ON
MATERNAL DIET THAT INCLUDES MILK
TO CUT THAT OUT AS A TRIAL,
OKAY?
OR SWITCH TO ANOTHER FORMULA
HYPO ALLERGENIC.
IT'S A SIGNIFICANT PROBLEM THAT
HAS A BIG SPECTRUM OF
PRESENTATION.
AND NEEDS TO BE ADDRESSED WITH
THAT IN MIND.
>> GREAT.
THANK YOU, EVERYONE.
THE NEXT QUESTION I HAVE IS
RELATED TO OF COURSE OUR TOPIC
BIOACTIVES.
AND IF YOU COULD PICK ONE
CATEGORY OF BIOACTIVES, THAT YOU
FEEL LIKELY HAS A BIG IMPACT ON
DEVELOPMENT BUT HAS NOT BEEN
STUDIED ENOUGH, WHAT WOULD IT
BE?
HOW WOULD YOU MEASURE ITS
FUNCTION AND SAFETY?
>> I CAN MAKE -- I MENTIONED
THERE'S PERHAPS SIGNIFICANT
RATIONALE FOR LOOKING AT WHETHER
FOOD PROTEIN SHOULD BE
INTRODUCED EARLIER, EVEN THAN
WHAT THE CURRENT GUIDELINES
MENTIONED.
AND WHETHER I THINK THE FIRST
STEP TO LOOK AT THIS OBVIOUSLY
WOULD BE TO LOOK AT WHAT ARE THE
NORMAL LEVELS OF FOOD ANTIGENS
IN BREAST MILK AND WHETHER
MATERNAL DIET AS IMPACT IN THAT
ARENA.
I THINK IT'S A SECONDARY
QUESTION TO ADDRESS WHETHER
THESE SHOULD BE ADDED, COULD BE
ADD, SHOULD NOT BE ADDED TO
FORMULAS.
SO I THINK THAT'S OBVIOUSLY A
SIGNIFICANT QUESTION.
>> I THINK ANOTHER AREA MAY BE
THE MICROBIAL THERAPEUTICS, AND
I HOPE MEGAN CAN ADD TO THAT A
LITTLE BIT.
A LOT OF THE STUDIES HAVE BEEN
DONE ON CERTAIN PROBIOTIC
BACTERIA OR CERTAIN PRE-BIOTICS,
BUT I THINK THAT THE APPROACH
MAY NOT BE NECESSARILY THE RIGHT
ONE IN TERMS OF LOOKING AT
OVERALL HEALTH OF THESE KIDS.
AND ONE OF THE THINGS MEGAN
BROUGHT UP ARE CERTAIN BIOTYPES
OF BACTERIA THAT DEVELOP IN THE
HEALTHY SITUATION VERSUS
UNHEALTHY SITUATION, AND NOT
JUST LOOKING AT THE BACTERIA
THEMSELVES BUT LOOKING AT THE
THEIR FUNCTION AND BY LOOKING AT
THEIR FUNCTION I'M NOT JUST
TALKING ABOUT METAGENOMICS BUT
COMBINATION OF THE MULTI-OMICS
AS I BROUGHT UP BEFORE.
>> YEAH, THAT'S LIKE AN
IMPOSSIBLE QUESTION I THINK.
THAT'S WHY I'M THINKING ABOUT
IT.
I MEAN, SO I DIDN'T TALK MUCH
ABOUT ALLERGY TODAY BUT ONE
INTERESTING ANALYSIS IN THE
CHILD COHORT TO LOOK AT THE
MATERNAL CONSUMPTION OF PEANUTS,
WHETHER OR NOT SHE WAS
BREASTFEEDING WHEN INTRODUCED TO
THE BABY, OBSERVATIONAL STUDY,
WE CAN'T DRAW FIRM CONCLUSIONS.
THE OVERALL SENSE WAS THAT WITH
MOM EATING PEANUTS AND
BREASTFEEDING AT THE TIME SHE
INTRODUCED PEANUTS, MAYBE
THERE'S COMPLEXES IN BREAST
MILK, IS THERE SOME WAY WE COULD
REPLICATE THAT IN FORMULA IS AN
IMPORTANT QUESTION.
AND TO JOE'S POINT I TOTALLY
AGREE ON THE MICROBIAL ASPECTS
OF MILK OR PRE AND PROBIOTIC
ASPECTS, MAKES SENSE WITH
INTEREST IN MICROBIOME.
THE MICROBES AND
OLIGOSACCHARIDES I DON'T THINK
THEY HAVE BEEN SELECTED FOR A
EVOLUTIONARY REASON, WHEN WE'RE
TALKING ABOUT INFANTS AT
SPECIFIC CRITICAL PERIOD OF
DEVELOP MAYBE WE SHOULD LOOK AT
HUMAN MILK FOR INSPIRATION ON
MICROBES IMPORTANT TO INCLUDE,
SAME THING FOR OLIGOSACCHARIDES,
AND LIKE JOE MENTIONED IT'S NOT
NECESSARILY ABOUT WHICH MICROBES
ARE THERE BUT WHAT ARE THEY
DOING AND CHAT WITH ANOTHER
SPEAKER MENTIONED LOOKING AT
METABOLOME, LIKE PRODUCTS OF
MICROBES, IN THE GUT AND IN
CIRCULATION, IS ANOTHER
IMPORTANT READOUT THAT MIGHT BE
MORE MEANINGFUL THAN WHICH
MICROBES AT THERE, GETTING AT
WHAT THEY ARE DOING, HOW IS THAT
GETTING INTO INFANT CIRCULATION,
SO WHAT I'M GOING TO ADD, A NEW
ELEMENT, I THINK WHAT'S MISSING
IS THE WHOLE APPROACH TO HUMAN
MILK RESEARCH LOOKING AT ONE
COMPONENT BY ONE COMPONENT, WE
NEED TO LOOK AT MILK AS A
BIOLOGICAL SYSTEM, THAT'S VERY
CHALLENGING EXPERIMENTALLY BUT
THINKING NOT ABOUT INDIVIDUAL
COMPONENTS, HOW THEY INTERACT,
THEY EXIST ALL TOGETHER, I THINK
SOME STUDIES, LOOKING AT
INTERNATIONAL STUDY, WITH DATA
SCIENTISTS USING ARTIFICIAL
INTELLIGENCE TO DO MULTI-OMICS,
COMBINE DATASETS AND SEE WHAT WE
CAN LEARN BY TAKING THOSE
APPROACHES, I THINK THAT'S
REALLY IMPORTANT MOVING FORWARD.
>> GREAT.
THANKS, APRIL.
FANTASTIC MODERATING.
THANK YOU TO THE FOUR SPEAKERS,
MANDY, MEGAN, JOE AND KIRSI.
SETTING THE STAGE AND KICKING US
OFF BUT FOR BEING AVAILABLE AND
PARTICIPATING IN THIS DISCUSSION
THAT WILL BE FORTHCOMING.
PART OF MY JOB IS TO BE
RESPECTFUL OF TIME.
WE'RE AT 12:36, WE DID GREAT.
GREAT FIRST SESSION, EVERYONE.
I WANT TO REMIND THOSE AGAIN, I
WILL APOLOGIZE FOR THE VIDEOCAST
GLITCH.
WE'VE BEEN REASSURED BY
PRODUCERS THE VIDEOCAST WILL BE
IN ITS ENTIRETY WHEN ON THE
WEBSITE SO ANYTHING MISSED WILL
BE AVAILABLE IN ITS ENTIRETY.
TO THE SPEAKERS, THANK YOU.
WE'LL BREAK AND RETURN AT 1:05
WELCOME, EVERYONE.
WE'RE PLEASED TO HAVE YOU HERE
WITH US.
THE FIRST SESSIONS WERE
INCREDIBLE, INSANE AMOUNT OF
INFORMATION FOR THE SHORT AFTER
AMOUNT OF TIME FOR THE WONDERFUL
SPEAKERS.
I'LL TURN IT OVER TO DR. ANDREW
BREMER AND DR. KOTARO KANEKO TO
TAKE OVER THE NEXT SESSION.
>> I WANT TO ECHO WHAT AN
AMAZING FIRST SESSION WE HAD.
I HAVE THE HONOR OF INTRODUCING
SESSION NUMBER 2, FOR THOSE WHO
DIDN'T SEE THE FIRST SESSION I'M
STILL DREW BREMER, STILL AT THE
NICHD.
I HAVE THE HONOR OF
CO-MODERATING WITH MY COLLEAGUES
DR. KOTARO KANEKO, CENTER FOR
FOOD SAFETY AND APPLIED
NUTRITION AT FDA.
THIS SESSION WILL COVER HOW
HUMAN MILK CAN BE USED AS
REFERENCE FOR FORMULA AND
CHALLENGES HAVING OF SAID
REFERENCE.
I WILL GIVE A BRIEF INTRODUCTION
OF THE SPEAKERS IN PRESENTATION
ORDER.
FULL BIOGRAPHIES ARE ON THE
WORKSHOP WEBSITES.
REMEMBER QUESTIONS AND COMMENTS
CAN BE SUBMITTED IN REAL TIME
THROUGHOUT THE SESSION.
I WANT TO SAY A PROFOUND THANK
YOU TO OUR AUDIENCE, WONDERFUL
QUESTIONS AND THEY ARE COMING
IN, WE CAN'T ADDRESS THEM ALL
BUT THEY ARE BEING CAPTURED AND
I APPRECIATE IT AND DO APOLOGIZE
FOR THE SNAFU BUT I WILL REMIND
FOLKS THE FINAL VERSION ALL THE
TALKS WILL BE THERE IN THEIR
ENTIRETY.
AFTER EACH OF THESE TWO TALKS,
WE'LL MODERATE A BRIEF QUESTION
AN ANSWER SESSION DEPENDING ON
TIME AVAILABLE.
FIRST SPEAKER IS DR. SHELLY
McGUIRE, UNIVERSITY OF IDAHO,
DIRECTOR AND PROFESSOR OF
NUTRITION, SCHOOL OF FAMILY AND
CONSUMER HEALTH AT UNIVERSITY OF
IDAHO, BACKGROUND IN HUMAN
PHYSIOLOGY AND NUTRITION,
EXPERTISE IN MATERNAL AND INFANT
NUTRITION, COMPOSITION,
ASSESSMENTS AND MICROBIOME.
SECOND IS DR. STEVE ABRAMS,
UNIVERSITY OF TEXAS AUSTIN,
PROFESSOR, RESEARCH ON THE
NUTRIENT NEEDS OF INFANTS AND
CHILDREN, SERVED AS MEMBER OF
THE COMMITTEE ON NUTRITION
AMERICAN ACADEMY OF PEDIATRICS,
CHAIR UNTIL FROM 2017, TO 2021
AND CO-AUTHOR OF THE A HANDBOOK
FOR PEDIATRICS.
FOR THE SAKE OF TIME, IT'S ALL
YOURS.
>> I THINK THAT'S UP.
THANK YOU ALL FOR INVITING ME TO
SPEAK.
IT'S HUMBLING TO SPEAK AFTER
THOSE GREAT TALKS THAT HAPPENED
EARLIER.
I'M SHELLY McGUIRE, UNIVERSITY
OF IDAHO, ASKED TO TALK ABOUT
HUMAN MILK AS OUR BEST YET DARN
TRICKY REFERENCE FOR NUTRIENT
INTAKES, AND ALSO WHAT ABOUT
BIOACTIVES, THAT MIGHT EVEN BE
TRICKIER.
HERE IS MY FUNDING AND
DISCLOSURES, GRATEFUL FOR ALL OF
THIS FUNDING, AND I HAVE NO
CONFLICTS OF INTEREST RELATED TO
THE TALK TODAY.
SO, ASIDE FROM TALKING ABOUT
MILK COMPOSITION AND ITS
VARIABILITY, OLD HAT TO MOST OF
THE SPEAKERS BUT MAYBE NOT TO
PARTICIPANTS, STEVE AND I WERE
ASKED TO TALK ABOUT A FEW
QUESTIONS THAT ASHLEY POSED MANY
WEEKS AGO.
I'M GOING TO HIT QUESTION 1, AND
THAT QUESTION IS HOW SHOULD
EXISTING DATA BE USED TO
EVALUATE SAFETY OF BIOACTIVE
INGREDIENTS WITH VARIABLE LEVELS
IN HUMAN MILK, FOR USE IN INFANT
FORMULAS AND TO DRILL DOWN MORE
WHAT IS THE BIOLOGICAL
SIGNIFICANCE OF CHANGES OR
DIFFERENCES IN LEVELS OF HUMAN
MILK CONSTITUENTS, WHAT ARE
POTENTIAL HEALTH RISKS FOR
INFANTS EXPOSED TO INGREDIENTS
THAT HAVE DYNAMIC SHIFTS IN
HUMAN MILK, AND NATURE OF
BIOACTIVES IN HUMAN MILK, CAN
DATA BE USED AS A REFERENCE FOR
INFANT FORMULA.
I'LL WARN YOU RIGHT NOW I'M NOT
REALLY GOING TO ANSWER THESE
QUESTIONS BUT WE'LL AT LEAST
ADDRESS THEM.
AND THERE'S MORE QUESTIONS ABOUT
SAFETY THAT STEVE AND OTHERS
WILL BE DEALING WITH AFTER MY
TALK.
I'D LIKE TO START TALKING ABOUT
HUMAN MILK, ACTUALLY JUST MILK
IN GENERAL AND WHY IS IT SO
SPECIAL.
AND AS YOU'VE HEARD, MILK IS A
SOLE SOURCE NUTRITION FOR
MAMMALIAN OFFSPRING, BUT IT'S
MORE THAN NUTRIENTS.
IT HAS MANY COMPONENTS INCLUDING
BIOACTIVES, THESE ARE PLAY
INDIVIDUAL ROLES AND MORE
IMPORTANTLY MULTIPLE ROLES AND
WE BELIEVE THEY WORK TOGETHER AS
A BIOLOGICAL SYSTEM WHICH IS
MENTIONED SEVERAL TIMES.
THIS IS A FIGURE, UNPUBLISHED,
FROM ONE OF THE UPCOMING BEGIN
REPORTS, IN WHICH WE ATTEMPTED
TO CLASSIFY ALL OF THE
INGREDIENTS IN HUMAN MILK,
BUCKETS OF INGREDIENTS, INTO
CATEGORIES THAT NOURISH AND
THAT'S USUALLY WHAT WE THINK
ABOUT WHEN WE THINK ABOUT MILK,
WE THINK ABOUT ESSENTIAL AN
NON-ESSENTIAL NUTRIENTS.
BUT THEY DO MORE THAN NOURISH.
SO THESE COMPONENTS ALSO PROTECT
THE INFANT WHICH YOU'VE HEARD A
LOT ABOUT, AND ALSO COMMUNICATE
INFORMATION TO THE INFANT THAT
INFORMATION CAN HELP THE INFANT
SURVIVE BEST IN A PARTICULAR
ENVIRONMENT.
AND AS YOU CAN SEE, THE
NUTRIENTS THAT WE THINK OF ARE
OFTEN THE NOURISH CATEGORY, BUT
THEY ARE ALSO IN OTHER
CATEGORIES.
WE BELIEVE THAT MOST OF THE MILL
COMPONENTS DO MULTIPLE THINGS.
AND I JUST WANTED TO POINT OUT
HERE THAT MANY OF THESE
COMPONENTS IN MILK ARE
BIOACTIVES, THEY ARE NOT WHAT WE
CONSIDER NUTRIENTS.
MAYBE IF WE CONTINUED TO STUDY
THEM, WE WOULD RECLASSIFY THEM
AS NUTRIENTS BUT RIGHT NOW THEY
ARE CONSIDERED TO BE BIOACTIVES.
SO YOU'VE HEARD ABOUT QUITE A
FEW OF THESE MICROBES, HMOs,
ET CETERA, ANTIBODIES, WE'LL
TALK MORE ABOUT THOSE IN THIS
TALK AND THEN IN LATER TALKS
TALK ABOUT HOW THEY DO
POTENTIALLY WORK TOGETHER.
SO WHY IS MILK SO TRICKY?
WELL, LIKE I SAID, THE SPEAKERS
HERE WILL KNOW THE ANSWER TO
THIS BUT FOR THOSE WHO HAVEN'T
THOUGHT OF MUCH ABOUT STUDYING
MILK, IT'S TRICKY TO STUDY.
COMPOSITION OF MILK VARIES A
LOT.
AND INCLUDING COMPOSITION OF
BIOACTIVES, AND IT'S NOT JUST
POPULATION DIFFERENCES.
THESE VARIABLES, THESE
COMPONENTS, CAN VARY IN TIME
POSTPARTUM, THEY CAN CHANGE OVER
A DAY, THEY CAN EVEN CHANGE
WITHIN A FEED.
THEY ARE AFFECTED, SOME ARE
AFFECTED, BY MATERNAL DIET,
MATERNAL NUTRITIONAL STATUS LIKE
BMI, HEALTH, STRESS, ET CETERA.
WE'RE NEVER GOING TO HAVE A
NUTRITION FACT PANEL FOR HUMAN
MILK LIKE WE HAVE FOR BOVINE
MILK, WHICH IS STANDARDIZED FOR
HOW MUCH FAT, PROTEIN AND EVEN
SOME OF THE MICRONUTRIENTS LIKE
VITAMIN D THAT IS IN COW'S MILK.
IT'S NEVER GOING TO HAPPEN FOR
HUMAN MILK.
WE HAVE THESE PERENNIAL
QUESTIONS.
FOR EXAMPLE, WHAT IS THE NORMAL
COMPOSITION OF HUMAN MILK?
THE ANSWER IS IT VARIES.
WE'LL TALK MORE IN THE NEXT FEW
MINUTES ABOUT THAT.
ALSO, THIS IS REALLY ACTUALLY
QUITE CRITICAL, IT'S ONE OF
THESE METHODOLOGIC THINGS THAT I
THINK UNLESS YOU'RE IN THE FIELD
YOU PROBABLY DON'T THINK ABOUT,
BUT WHAT IS ACTUALLY A
REPRESENTATIVE MILK SAMPLE?
IF MILK COMPETITION CHANGES IN A
FEED, OVER A DAY, WITH ALL OF
THESE OTHER FACTORS HOW DO WE
TAKE A MILK SAMPLE OR MULTIPLE
SAMPLES THAT REPRESENT WHAT IS
NORMAL.
WE WILL COME BACK TO THAT WITH
AN EXAMPLE.
ALSO, ARE THERE ADAPTIVE
CONSEQUENCES TO ALL OF THIS
VARIATION, OR IS IT JUST RANDOM
AND DOESN'T MATTER?
OR IS IT ACTUALLY ONE SIZE FITS
ALL COMPOSITION OR IS OPTIMAL
MILK COMPOSITION DIFFERENT AMONG
WOMEN AND ACROSS POPULATIONS?
AND FINALLY, WHAT MAKES THIS
TRICKY IS MILK IS A COMPLEX
FLUID, IT'S REALLY DIFFICULT TO
ANALYZE.
AND SO ALL METHODS THAT WE USE
TO ANALYZE MILK HAVE TO BE
VALIDATED AND OPTIMIZED FOR
MILK, AND IN SOME CASES FOR
HUMAN MILK BECAUSE COMPONENTS
ARE QUITE DIFFERENT BETWEEN
HUMAN MILK AND OTHER MILK TYPES
WHICH WE'LL GO INTO IN THE NEXT
FEW SLIDES.
SO, IT'S TRICKY.
BUT IT'S IMPORTANT.
MILK COMPOSITION IS IMPORTANT,
UNDERSTANDING MIGHT BE ONE OF
THE MOST IMPORTANT THINGS WE CAN
DO FOR THE ENTIRE FIELD OF
NUTRITION TO TELL YOU THE TRUTH.
HUMAN MILK IS THE ONLY FOOD
DESIGNED BY MOTHER NATURE TO
FEED HUMANS, EVERYTHING ELSE WE
EAT WE'VE CO-OPTED FROM THE
ENVIRONMENT OR WE'VE JUST
CREATED OURSELVES.
BUT HUMAN MILK IS A SPECIAL,
SPECIAL FOOD.
IT IS CERTAINLY OUR BEST GUESS
AS TO WHAT INFANTS REQUIRE, AND
THEREFORE WHAT THEY SHOULD BE
FED.
I THINK THERE'S NO QUESTION
ABOUT THAT.
THESE BEST GUESSES UNDERLIE
NUTRIENT INTAKE GUIDANCE FOR
INFANTS.
FOR EXAMPLE, THE DIETARY
REFERENCE INTAKES IN WHICH
ADEQUATE INTAKE OR A.I. LEVELS
FOR INFANTS HAVE BEEN DERIVED
FROM MULTIPLYING THE AVERAGE
NUTRIENT CONCENTRATION IN MILK
BY THE AVERAGE MILK CONSUMPTION
FROM TWO TO SIX MONTHS OF LIFE.
MANY OF THESE VALUES WERE
INFORMED BY LESS THEN TEN MILK
SAMPLES, ALL DATA DECADES OLD AT
THIS POINT.
THERE'S A CRITICAL NEED TO
UPDATE THESE VALUES, USING MILK
COMPOSITION AND CONSUMPTION DATA
FROM THE SAME MATERNAL-INFANT
DYAD RATHER THAN ASSUMING ALL
CONSUME THE SAME AMOUNT, AND WE
NEED DO THAT IN A CONTEMPORARY
WAY.
WE USE VALUES FOR MILK
COMPOSITION, THEY INFORM THE
DRIs AND THEREFORE DIETARY
GUIDELINES FOR AMERICANS WHICH
AS YOU KNOW NOW INCLUDES
INFANTS.
THIS IS COMPLICATED FOR
BIOACTIVES BECAUSE BY DIVERSITY
NEGATIVES BIOACTIVES ARE NOT
TECHNICALLY REQUIRED, THEREFORE
THERE ARE NO DRI VALUES SO WE'RE
IN A BIT OF A WILD WEST IN TERMS
OF TRYING TO UNDERSTAND WHAT'S
NORMAL AND WHAT SHOULD INFANTS
CONSUME BECAUSE THESE ARE NOT
CONSIDERED REQUIRED COMPONENTS.
SO, WHY IS HUMAN MILK SO
SPECIAL?
WE LIKE TO THINK THAT ITS
COMPOSITIONS THAT EVOLVED OVER
THE MILLENIA, IN SUCH A WAY THAT
THAT HAS BEEN DRIVEN BY
SELECTIVE PRESSURES.
HOWEVER, WE HAVE VERY LITTLE
EVIDENCE TO SUPPORT THAT.
I'LL SHOW ONE PIECE OF EVIDENCE
IN A FEW SLIDES.
BUT THIS IDEA THAT MILK HAS
EVOLVED TO NOURISH, PROTECT, AND
COMMUNICATE TO THE HUMAN INFANT
IS PROBABLY TRUE BUT WE HAVE
VERY LITTLE EMPIRICAL DATA TO
SUPPORT THAT.
HOWEVER, WE DO KNOW HUMAN MILK
COMPOSITION IS QUITE DIFFERENT
FROM MILKS PRODUCED BY OTHER
MAMMALS, AND THIS IS A LITTLE
BIT BITTY TABLE FROM A NICE
REVIEW THAT WAS PUBLISHED A
COUPLE YEARS AGO, OR LAST YEAR I
GUESS IN FRONTIERS IN NUTRITION,
COMPARING THE MAJOR COMPONENTS
OF MILK PRODUCED BY VARIETY,
HUMANS ON THE RIGHT SIDE, THAT'S
OUR TYPE OF MILK OF INTEREST,
AND I'LL COMPARE THIS TO BOVINE
MILK, OVER HERE ON THE LEFT.
WITHOUT GOING INTO DETAIL HERE,
IT'S VERY WELL DOCUMENTED THAT
PROTEIN CONTENT OF HUMAN MILK IS
IRE, LACTOSE IS HIGHER,
OLIGOSACCHARIDES ARE QUITE A BIT
HIGHER, ASSUMING THAT HAS BEEN
EVOLUTIONARY DRIVEN.
PROTEIN, THE WORD ENCOMB
PASS -- ENCOMPASSES OTHER TYPES
OF PROTEINS, I WANT YOU TO
CONSIDER IS PROTEIN A NUTRIENT,
BIOACTIVE OR BOTH? IF WE DELVE
DEEPER INTO DATA COMPARING
DIFFERENT TYPES OF PROTEINS OR
DIFFERENT I SHOULD SAY PROTEIN
FRACTIONS, MAJOR PROTEIN
FRACTIONS IN MILK, WE BASICALLY
HAVE THE CASEINS AND WHEY
PROTEINS.
MOST CLASSIFICATIONS ARE QUITE A
BIT LOWER IN HUMAN THAN BOVINE
MILK, ACROSS THE BOARD IN TERMS
OF CATEGORIES, ALPHA LACTO, THAT
IS HIGHER IN HUMAN MILK.
A PAPER WAS PUBLISHED LOOKING AT
HUMAN MILK SAMPLES FROM SEVEN
WOMEN AND BULK TANK MILK SAMPLES
FROM COWS, GOATS, YAKS, SKIM
MILK FRACTION, LOST ALL THE
PROTEINS IN THE MILK VOLUME
MEMBRANE, WANT TO SHOW YOU ONE
FIGURE FROM THIS PUBLICATION
WHERE WE'RE LOOKING AT THE
NUMBER OF PROTEINS THAT WERE
IDENTIFIED USING PROTEOMICS IN
THE FOUR TYPES OF MILK, YOU CAN
SEE HERE THERE WERE 65 PROTEINS
IN THE MIDDLE OF THIS DIAGRAM,
65 THAT ALL THE MILK TYPES
CONTAINED.
BUT HUMAN MILK CONTAINED 77
UNIQUE PROTEINS, SHOWN BY OTHERS
AS WELL.
THESE UNIQUE PROTEINS INCLUDED
THINGS LIKE SALT ACTIVATED AND
IMMUNOGLOBULIN J CHAIN WHICH
PROBABLY AREN'T BIG SURPRISES
BUT THIS GOES TO SHOW THERE ARE
SPECIFIC MILK PROTEINS THAT ARE
UNIQUE TO HUMAN MILK.
AND THAT MILK PROTEIN PROVIDES
MUCH MORE THAN JUST ESSENTIAL
ACIDS, AMINO ACIDS, AND SOURCE
OF ENERGY.
THERE ARE A LOT OF POTENTIAL
BIOACTIVES IN THE MILK PROTEIN
FRACTION.
WHAT IS NORMAL?
IF WE LOOK AT A.I. VALUES, A.I.
FOR INFANTS FOR PROTEIN IS .91
GRAMS PER DAY DERIVED ON AVERAGE
MILK INTAKE OF 780 MILLS PER
DAY, AVERAGE OR NORMAL PROTEIN
CONTENT OF HUMAN MILK WHICH
DECLARED TO BE 11.7 GRAMS PER
LITER.
WE HAVE RECENTLY CONDUCTED A
STUDY, INSPIRE STUDY, THAT GOES
BY THE TITLE OF WHAT'S NORMAL.
THIS STUDY WAS DESIGNED TO
ACTUALLY TRY TO FIGURE OUT
WHAT'S NORMAL MILK MICROBIOME
AROUND THE WORLD.
WE ALSO HAVE PROTEIN DATA FROM
THIS STUDY.
THIS WAS A CROSS-SECTIONAL
EPIDEMIOLOGIC STUDY.
WE HAD 11 COHORTS IN 8 COUNTRIES
AROUND THE WORLD.
IN THE END WE STUDIED 412
RELATIVELY HEALTHY MOMS AND
BABIES BETWEEN 1 AND 3 MONTHS
POSTPARTUM, COLLECTED
CONVENIENCE SAMPLES MOSTLY FOR
MILK, TWO HOURS SINCE LAST
FEEDING IN THE MORNING.
WE STANDARDIZED COLLECTION
RIGOROUSLY FOR THIS STUDY.
AND WE ALSO STANDARDIZED MILK
HOW IT WAS SHIPPED TO THE UNITED
STATES AND HOW IT WAS ALSO
ANALYZED.
I WANT TO SHOW YOU THE MILK
PROTEIN VALUES FROM THIS STUDY
TO MAKE THE POINT.
THESE ARE THE MEAN PROTEIN
VALUES, IN THE COHORTS FROM THE
LEFT TO RIGHT, THIS IS RURAL
ETHIOPIA, TO CALIFORNIA AND
WASHINGTON STATE COHORT.
YOU CAN SEE THERE'S QUITE A BIT
OF VARIABILITY IN TERMS OF
WHAT'S NORMAL.
IF I SUPERIMPOSE THE A.I. VALUE
USED FOR A.I.s HERE YOU CAN
SEE IT'S VERY SIMILAR TO WHAT WE
FOUND IN WASHINGTON STATE,
WASHINGTON AND IDAHO, AND
INTERESTINGLY ALL THE VALUES
USED TO SET THE A.I. WERE FROM
MILK SAMPLES COLLECTED IN
CALIFORNIA AND COLORADO.
SO MAYBE THIS SHOULDN'T BE A BIG
SPRY. -- SURPRISE.
IN MOST THE PROTEIN IS HIGHER.
BOTTOM LINE NORMAL VARIES.
YOU'LL HEAR THAT MORE THAN ONCE.
THE UNKNOWNS REMAIN DOES THIS
MATTER?
DOES THIS VARIABILITY MATTER?
ALSO WOULD THIS BE WASHED OUT IF
WE COLLECTED FOR MILK
CONSUMPTION?
AND ARE THE PROTEIN PROFILES
DIFFERENT?
WE DON'T KNOW THE ANSWERS TO
THOSE QUESTIONS.
EVEN MORE BASIC, JUST TO MAKE
THE POINT I WANT TO ASK THE
QUESTION WHAT IS A
REPRESENTATIVE SAMPLE FOR MILK
PROTEIN AND DID WE EVEN COLLECT
A REPRESENTATIVE SAMPLE?
WE HAVE RECENTLY DESIGNED A
STUDY TO UNDERSTAND WHAT'S
REPRESENTATIVE SAMPLE FOR MILK
MICROBIOME, IN THE PROCESS OF
DOING THAT WE ALSO ANALYZED MILK
SAMPLES FOR PROTEIN.
THE DOGMA HERE IS THAT IT
DOESN'T MAT WHATEVER KIND OF
MILK SAMPLE YOU TAKE, ANY TIME
OF DAY, MILK PROTEIN DOESN'T
VARY THAT MUCH.
IN THIS STUDY WE RECRUITED 17
HEALTHY BREASTFEEDING MOMS,
COLLECTED FORE, MID, HIND, LEFT
AND RIGHT BREAST, AND USING
COMPLETE BREAST EXPRESSION
BEGINNING AT 5 A.M.
TWO FIGURES, IT TURNED OUT TO BE
MORE COMPLICATED THAN WE HAD
ANTICIPATED WITH PROTEIN.
THIS IS A FIGURE COMPARING
FOREMILK TO MID-MILK, AND HIND
MILK, 5% DIFFERENCE,
SIGNIFICANT, SUGGESTING PERHAPS
WE NEED TO TAKE COMPLETE BREAST
EXPRESSION LOOKING AT TOTAL
PROTEIN.
WE FOUND THIS FROM MORNING TO
EVENING, THIS IS HIGHLY
SIGNIFICANT, 10% INCREASE FROM
MORNING UNTIL EVENING.
SO, MILK PROTEIN NORMAL DOES
VARY WITHIN A FEED, OVER A DAY.
WE NEED TO START PAYING TO THAT
PROBABLY.
DOES IT MATTER FOR INFANT
HEALTH?
WE DON'T KNOW.
AND ARE THESE GLOBAL CHANGES IN
ALL PROTEINS OR ENRICHMENT OF A
SUBSET OF PROTEINS LIKE ALL OF
THOSE BIOACTIVEES WE TALKED
ABOUT SOONER.
DID THEY CHANGE OVER FEED, OVER
A DAY, WE DON'T KNOW.
ANOTHER QUICK EXAMPLE I WANT TO
GIVE YOU, AND A THEME THROUGHOUT
THE DAY HUMAN MILK
OLIGOSACCHARIDES FROM THE
INSPIRE STUDY, THIS
INTERNATIONAL EPIDEMIOLOGIC
STUDY.
THESE DATA WERE COLLECTED WITH
THE GREAT HELP OF OUR COLLEAGUE
WHO IS AN EXPERT ON HMO ANALYSES
AND THESE ARE THE SAME COHORTS
ON THE X-AXIS WITH HMO
CONCENTRATION ON THE Y-AXIS,
STACKED BAR CHARTS, EACH COLOR
IN THE BAR REPRESENTS DIFFERENT
TYPE OF HMO, AND AS MEGAN
MENTIONED OVER 100 HMO TYPES IN
MILK.
A COUPLE QUICK TAKEHOME
MESSAGES, TOTAL HMO
CONCENTRATION VARIES AROUND THE
WORLD, VARIES AMONGST THESE
COHORTS, ALSO IF YOU WERE TO
LOOK AT DISTRIBUTION OF THE
VARIOUS HMOs THAT PROFILE ALSO
VARIES AROUND THE WORLD.
AND STEVE AND OTHERS WILL BE
SPENDING MORE TIME TALKING ABOUT
POTENTIAL IMPLICATIONS AND
ADDITIONAL STUDIES RELATED TO
ADDITION OF HMO IN FOLLOWING
PRESENTATIONS, I JUST WANTED TO
GIVE A HEADS-UP HMO IS QUITE
VARIABLE.
WE'VE DONE QUITE A BIT OF WORK
TRYING TO UNDERSTAND THIS
VARIABILITY AND I WANT TO SHOW
YOU ONE SLIDE HERE THAT TAKES
THIS IDEA OF WHETHER MILK HAS
BEEN SELECTED EVOLUTIONARYILY,
WE GENOTYPED, USING A
MULTI-ETHNIC GLOBE ARRAY,
1.7 MILLION SNPs, ABLE TO
EVALUATE WHETHER THE PRESENCE OR
ABSENCE OF VARIOUS SNPs OR
SINGLE NUCLEOTIDE POLYMORPHISM
WAS RELATED.
I'M SHOWING ONE MANHATTAN PLOT,
WHICH IS BASIC OUTPUT FROM THIS
SORT OF GWAS STUDY LOOKING AT
VARIATION IN THOSE 1.7 MILLION
SNPs, WHICH ARE FOUND ON ALL
OF THESE CHROMOSOMES, SO THE
X-AXIS REPRESENTS ALL THE
CHROMOSOMES AND EACH OF THE
COLORS, EACH OF THE DOTS
REPRESENTS THE SNPs, WHERE
THEY ARE LOCATED ON THE
CHROMOSOME.
THE WAY THAT YOU INTERPRET
MANHATTAN PLOT IF ONE OF THE
DOTS, AND WHAT WE'RE LOOKING AT
HERE IS WHETHER THOSE SNPs ARE
RELATED TO IN THIS CASE 2 FL
CONCENTRATION IN THE MILK AND IF
DOTS OR SNPs ARE ABOVE THE RED
LINE WE SAY THEY ARE
SIGNIFICANTLY RELATED TO
VARIATION IN 2FL, A LOT OF
SNPs ON CHROMOSOME 19 THAT
WERE RELATED TO 2FL, THAT WASN'T
A BIG SURPRISE BECAUSE
CHROMOSOME 19 IS THE LOCATION OF
THE GENE NEEDED TO SYNTHESIZE
2FL AND OTHER HMOs, ALSO ABLE
TO LOOK AT INDIVIDUAL SNPs SO
EACH ONE OF THESE FIGURES HERE
REPRESENTS A DIFFERENT SNP, THAT
WAS SIGNIFICANTLY RELATED TO 2FL
CONCENTRATION, AND ALONG THE
X-AXIS YOU CAN SEE WHETHER THE
WOMAN WAS HOMOZYGOUS OR
HETEROZYGOUS, AND MILK
COMPOSITION VARIED.
WE USED EVOLUTIONARY STATISTICS,
THIS ONE I'M SHOWING HERE IS A
WAY TO ACTUALLY LOOK AT WHETHER
EVOLUTIONARY SELECTIVE PRESSURES
WERE LIKELY INVOLVED IN THESE
SNPs, AND WE FOUND VERY STRONG
EVIDENCE OF SELECTIVE EVOLUTION.
EVOLUTION SELECTION DOES SEEM TO
HAVE BEEN INVOLVED.
DOES THIS MATTER?
WE DON'T KNOW.
SHOULD INFANTS WITH DIFFERENT
GENOTYPES CONSUME MILK WITH
DIFFERENT HMO PROFILES?
WE DON'T KNOW THE ANSWER TO THAT
AS WELL.
AND THEN FINALLY JUST A LITTLE
BIT ABOUT MILK MICROBIOME.
I WANT TO SHOW DATA FROM THE
INSPIRE STUDY, IN THIS CASE
STACKED BAR CHARTS FOR THE
DIFFERENT BACTERIAL GENERA THAT
ARE IN MILK ACROSS ALL OF THESE
DIFFERENT POPULATIONS THAT I
ALREADY KIND OF TALKED THROUGH.
YOU CAN SEE THAT IN FACT THE
MICROBIOME PROFILES ARE
DIFFERENT AROUND THE WORLD, SOME
COHORTS SEEM SIMILAR BUT IN
GENERAL THERE'S A LOT OF
VARIABILITY HERE.
I WANT TO POINT OUT INTERESTING
THINGS HERE.
RURAL ETHIOPIA MAJOR TAXON, WE
THINK IT WAS GETTING IN THE BILK
BECAUSE WOMEN EAT A LOT OF A
STAPLE FOOD WHICH IS FERMENTED
IN THE GROUND AND THERE'S SOME
GOOD -- VERY GOOD EVIDENCE THAT
BACTERIA ARE TRAFFICKED FROM THE
MATERNAL G.I. TRACT TO THE
MAMMARY GLANDS, INTERESTINGLY IN
GHANA WE HAD HIGH LEVELS OF
LACTOBACILLUS, WE THINK OF THAT
AS HEALTHY PROBIOTIC AND HIGH
LEVELS OF KLEBSIELLA WHICH WE DO
NOT THINK OF AS HEALTHY
PROBIOTIC BUT NOT ASSOCIATED
WITH NEGATIVE HEALTH OUTCOMES IN
THIS CASE.
AGAIN, THE MICROBIOME VARIES.
WHAT SHOULD BE ADDED?
THAT QUESTION HAS COME UP.
ARE THE SAME BACTERIA BENEFICIAL
IN ALL LOCATIONS AND CULTURES,
IS THERE A ONE-SIZE-FITS-ALL
CONSTRUCT HERE THAT WE MIGHT BE
ABLE TO APPLY TO FORMULA, WE
DON'T KNOW THE ANSWER TO THAT.
IF WE GO BACK TO THE INITIAL
QUESTIONS ASHLEY POSED, I WANT
TO COMMENT ON THE THREE IN MINE
SECTION.
THE FIRST WAS WHETHER IS THE
BIOLOGICAL SIGNIFICANCE OF
OBSERVED CHANGES OR DIFFERENCES
IN LEVELS OF VARIOUS HUMAN MILK
CONSTITUENTS, AND I WOULD SAY
WE'RE STILL IN THE DISCOVERY
PHASE HERE.
I THINK THERE IS REASON TO
BELIEVE SOME OF THE DIFFERENCES
ACROSS POPULATIONS MAY HAVE BEEN
DRIVEN BY EVOLUTIONARY
PRESSURES, WE NEED TO DO MORE
GWAS SORT OF STUDIES IN ORDER TO
EVALUATE THAT.
I ALSO THINK WE NEED STUDIES
RELATING VARIATION WITH
VARIATION IN INFANT OUTCOMES.
WE'VE TALKED EARLIER, MANDY
TALKED ABOUT IMPORTANCE OF
STUFFEDDIES WITH FORMULA
FORTIFIED WITH DIFFERENT LEVELS
OF BIOACTIVES BUT WE CAN ALSO
LOOK AT THIS IN A NATURAL
SITUATION WHERE WE HAVE THIS
VARIABILITY AND WE CAN START
LOOKING AT WHETHER THERE ARE
ASSOCIATIONS WITH INFANT HEALTH.
SECONDLY WHAT ARE POTENTIAL
RISKS FOR INSTANTS EXPOSED TO A
CONSTANT LEVEL OF BIOACTIVE
INGREDIENTS?
AND, AGAIN, WE'RE STILL IN THE
DISCOVERY PHASE.
BUT I WILL SAY THAT, YOU KNOW,
MANY INFANTS HAVE BEEN FED
PUMPED OR FROZEN OR BANKED MILK
FOR A VERY LONG PERIOD OF TIME
SO THEY EXPERIENCE THIS
PHENOMENA OF HAVING CONSTANT
LEVELS OF THESE COMPONENTS IN
WHAT THEY ARE CONSUMING AND WE
DON'T KNOW OF NEGATIVE OUTCOMES,
IT DOESN'T MEAN THEY ARE NOT
THERE BUT IT DOES SUGGEST THAT
MAYBE THE OUTCOMES WOULD BE
MINIMAL.
STILL UP IN THE AIR ON THAT ONE.
AND THEN FINALLY GIVEN THE
DYNAMIC FEATURE OF BIOACTIVE
CONSTITUENTS FROM DATA BE USED
AS REFERENCE FOR INFANT
FORMULATION, I THINK IT HAS TO
BE.
IT'S OUR BEST GUESS.
BUT I DO THINK IT'S PROBABLY
TIME THAT WE START EXAMINING THE
POTENTIAL IMPACTS OF THIS
VARIATION EXPERIMENTALLY BOTH IN
BREASTFED INFANTS AND
FORMULA-FED INFANTS.
WITH THAT, I AM DONE AND I WOULD
BE VERY HAPPY TO ANSWER ANY
QUESTIONS NOW OR AFTER STEVE'S
TALK.
>> THANK YOU, SHELLY FOR YOUR
THOUGHTFUL PRESENTATION.
BECAUSE WE ASKED YOU AND STEVE
SOME HARD, CHALLENGING
QUESTIONS, IN TERMS OF TIME, WE
WERE TIGHT SO AS MUCH AS WE HAVE
A LOT OF QUESTIONS I WANT TO
JUST TAKE JUST ONE QUESTION AND
THEN GIVE STEVE MORE TIME TO
FINISH.
SHELLY, THE WAY I THINK OF WHAT
YOU'VE TALKED ABOUT, I THINK WE
TAKE A LOT OF SNAPSHOTS WHEN
WE'RE TALKING ABOUT HUMAN MILK
COMPOSITION.
IT'S NOT ALWAYS CLEAR, HOW TO
INTERPRET EXISTING DATA BECAUSE
WE DON'T OFTEN PAY ATTENTION
UNTIL RECENTLY HOW AND WHERE AND
WHEN THE SAMPLES WERE TAKEN.
SO, YOU KNOW, WHAT ARE YOUR
THOUGHTS AS TO THE MOST
IMPORTANT ASPECTS IN TERMS OF
DATA COLLECTION ANALYSIS,
HOPEFULLY GIVE US A MEANINGFUL
AND REPRESENTATIVE DATASET THAT,
YOU KNOW, WE CAN HOPEFULLY USE
AS A REFERENCE IN TERMS OF WHAT
WE USED TO DO AND WHAT WE SHOULD
BE THINKING ABOUT IN THE FUTURE
IN TERMS OF COLLECTING DATA?
>> YEAH, GOOD QUESTION.
THESE AREN'T NEW OBSERVATIONS.
PEOPLE HAVE KNOWN MILK
COMPOSITION VARIES AND WERE
LOOKING AT REPRESENTATIVE SAMPLE
IN THE 1970s.
THIS ISN'T NEW.
DEPENDING ON THE COMPONENT THAT
YOU'RE LOOKING AT, I MEAN,
SOMETIMES YOU CAN JUST TAKE A
SPOT SAMPLE AND IT'S FINE.
SO FOR THOSE COMPONENTS, YOU
KNOW, THE DATA, AS LONG AS THE
REST OF THE METHODS WERE
ADEQUATE, THE DATA AND
LITERATURE ARE FINE.
WE'RE JUST LEARNING THAT SOME
OTHER COMPONENTS MAYBE -- WE
HAVE TO PAY ATTENTION, MILK
RECORDS ARE A GREAT EXAMPLE OF
THAT.
FATTY ACIDS ARE A GREAT EXAMPLE.
THE PROTEIN ISSUE SURPRISED ME
THAT WE FOUND A DIFFERENCE OVER
A FEED AND DAY.
IT WOULD BE HELPFUL TO DO
SYSTEMATIC REVIEW OF WHICH OF
THE ASPECTS IMPACT MILK
COMPOSITION AND WE NEED TO PAY
ATTENTION AS WE GO FORWARD.
A LOT OF RESEARCHERS DO.
A LOT OF RESEARCHERS IN THE
FIELD KNOW THIS, THEY PAY
ATTENTION TO IT, AND THEY DO
TAKE GOOD REPRESENTATIVE MILK
SAMPLES.
>> THANK YOU, SHELLEY.
STEVE, I DON'T WANT TO TAKE MORE
TIME AWAY FROM YOU SO LET'S GET
ON WITH YOUR PRESENTATION
HOPEFULLY WE'LL HAVE A FEW
MINUTES TO BRING BOTH OF YOU
BACK.
>> THANK YOU.
I APPRECIATE THE OPPORTUNITY TO
SPEAK TODAY.
I THINK MY ROLE IN THIS IS TO
BRING UP SOME OF THE QUESTIONS
AND CHALLENGES AND USING HUMAN
MILK AS A REFERENCE AND BRING UP
SOCIAL DIE DYNAMICS.
AND THEN LOOK AT ASSESSMENT
ISSUES, SAFETY BENEFIT,
LIMITATIONS, CURRENT DATA, USE
OF THESE TYPES OF DATA AND
SUMMARY AND RESEARCH
REQUIREMENTS.
SO, I THINK WE ALL KNOW WE'RE
TALKING ABOUT BIOACTIVES, A
LARGE NUMBER OF CATEGORIES, NOT
ALL ARE BRAND NEW IN TERMS OF
THINKING ABOUT THEM FOR USE IN
INFANT FORMULA, FOR EXAMPLE.
THE POSSIBILITIES OF USING
LACTOFERRIN HAS BEEN AROUND
SINCE THE 1980s, PERHAPS
SOONER THAN THAT.
I WORKED IN THE FIELD IN THE
1980s.
THIS IS NOT ENTIRELY NEW.
WE TALK ABOUT OLIGOSACCHARIDES,
THEY COME IN A LOT OF SOURCES
AND FORMS.
THERE'S A LOT OF OTHER ISSUES.
BIOACTIVES ARE OUT THERE, THAT
THE FDA HAS TO DEAL WITH.
THIS IS A LARGE AND COMPLEX
FIELD.
WE FOCUS ON THE HUME -- HUMAN
MILK OLIGOSACCHARIDES.
THIS WONDERFUL SLIDE REMINDS US
OF THE SEQUENCE, FACTORS WHICH
AFFECT HUMAN MILK, REFLECTED IN
THE MACRO AND MICRO NUTRIENT AND
BIOLOGICAL COMPOSITION OF IT
WHICH INCLUDES BIOACTIVES, WHICH
THEMSELVES HAVE A VARIETY OF
OUTCOME FUNCTIONS BUT WE NEED TO
THINK ABOUT AND BE SURE AS WE
TALK ABOUT THEM THAT WE'RE
TALKING ABOUT ALL THESE ISSUES
GROWTH, MICRONUTRIENTS, MARROW
DEVELOPMENT, IMMUNE SUPPORT.
IT'S A BROAD FIELD.
A LOT OF DIFFERENT TOPICS.
LET'S GET DOWN TO THE MEAT OF
IT.
SO WHEN WE TALK ABOUT THE
ADDITION OF BIOACTIVE FORM,
MANY, NOT ALL, ARE APPROVED VIA
THE GRAS PROCESS, GENERALLY
RECOGNIZED AS SAFE PROCESS.
SOME THINGS HAVE GONE THROUGH,
ADDITION OF DHA TO FORMULA,
OTHER COMPONENTS ARE
GRANDFATHERED IN FROM ORIGINS OF
THE PROCESS, FOR EXAMPLE
CARRAGEENAN.
JUST BECAUSE SOMETHING IS
PERCEIVED AS BEING SAFE DOESN'T
MEAN THE WHOLE WORLD HAS TO
AGREE UPON THAT.
I'M NOT HERE TO CRITICIZE OR
JUST GO THROUGH DETAILS OF PROS
AND CONS OF GRAS PROCESS OTHER
THAN TO SAY IT HAS LIMITATIONS
IN TERMS OF POTENTIAL BIAS AND
DATA SOURCES.
THE FDA SPENT TIME REVIEWING
DATA FROM THE GRAS PROCESS
MAKING ITS DETERMINATION, BUT
THE PROCESS ITSELF IS PERHAPS
ONE THAT NEEDS TO BE LOOKED AT
AS WE TALK ABOUT A LOT OF
COMPONENTS REALLY I'M NOT SURE
THE PROCESS EXISTS IT'S DESIGNED
TO COVER.
WHEN NATURE CHANGES, FORMULA
REQUIRES SIGNIFICANT EVALUATION
WHICH MAY INCLUDE GROWTH
MONITORING STUDIES THESE
THEMSELVES ARE CHALLENGING,
MONITORING TENDS TO BE
RELATIVELY SHORT TERM.
PERHAPS MORE SIGNIFICANT CONCERN
TO ME AS NEONATOLOGIST FORMULAS
ARE BEING USED, DESIGNED FOR
FULL-TERM INFANTS, ALSO WIDELY
USED FOR LATE PRE--TERM INFANTS.
AT TIMES EVEN AFTER A PERIOD OF
TIME FOR SMALLER PRE-TERM
INFANTS AND MONITORING STUDIES
ALMOST ENTIRELY WILL INCLUDE
LATE PRE-TERM INFANT,
REPRESENTING ABOUT 10 TO 12% OF
INFANTS BORN IN THE UNITED
STATES, NOT ALL WILL GET
FORMULA.
FURTHERMORE SGA, INTRAUTERINE
BIRTH INFANTS ARE NOT INCLUDED
IN SOME OF THESE STUDIES, GLOBAL
BASIS, MANY ARE BORN IN THESE
CATEGORIES, THAT'S LESS COMMON
IN THE UNITED STATES.
IT'S AN IMPORTANT CONSIDERATION.
WE THINK ABOUT GROWTH AND
BIOCHEMICAL STUDIES, WHAT ARE IS
THE STANDARD.
IN FACT, BREAST AND FORMULA FED
BABIES HAVE DIFFERENT GROWTH
RATES AND PROCESSES.
GLOBAL MONITORING STUDIES HAVE
SHOWN GROWTH IS GENERALLY
CONSISTENT THROUGHOUT THE WORLD,
WHEN INFANTS ARE FED PROPERLY,
BUT THERE ARE DIFFERENCES THAT
DEVELOP OVER TIME, AND THEREFORE
WE HAVE TO DECIDE WHAT IS OUR
STANDARD.
IS THE STANDARD THAT'S BEEN USED
FOR THE EXCLUSIVE BREASTFED BABY
APPROPRIATE FOR FORMULA FED
BABY?
AND DO WE TAKE INTO ACCOUNT
FORMULA FED BABIES ARE OFTEN FED
HIGHER VOLUME OF FORMULA THAN
BREASTFED BABIES RECEIVE IN
VOLUME IN HUMAN MILK ESPECIALLY
AFTER FIRST COUPLE MONTHS OF
LIFE.
WHICH ONES CAN BE GONE THROUGH A
MORE LIMITED BIOCHEMICAL
ASSESSMENT, WHICH REQUIRE MORE
SIGNIFICANT ANALYSIS ARE THINGS
THAT NEED TO BE CONSIDERED.
CONSIDERING CURRENT DATA ON
BIOACTIVES, DR. BELFORT DID A
GREAT JOB OF TALKING ABOUT
DEVELOPMENTAL EFFECTS, AND USING
A LARGE NUMBER OF MODALITIES
POINT OUT SPECIFICALLY THAT MANY
STUDIES LOOKED AT LONG-TERM
NEUROCOGNITIVE OUTCOMES FOCUSED
ON 18, 24 MONTH, BAILEY AND
SIMILAR SCORES THAT MAY NOT BE
IDEAL FOR ASSESSING SMALL OR
LONG-TERM EFFECTS OF BIOACTIVES,
WE NEED TO BE CAUTIOUS OF
DROPOUT RATES, AND THINGS THAT
CONFOUND STUDIES ALLOWING FOR
POSITIVE AND NEGATIVE EFFECTS TO
BE COMPLETELY MISSED BECAUSE OF
THESE PROBLEMS WITH THE STUDIES,
AS WELL AS IMPOSSIBILITY OF
TRULY BLINDING AND RANDOMIZING
STUDIES.
ALSO ENVIRONMENTAL STIMULI AND
FAMILY DYNAMICS ARE NOT FULLY
ASSESSED.
NUTRIENT INTERACTIONS WHICH
WE'LL TALK ABOUT A LITTLE BIT
ARE NOT ASSESSED, AS I POINTED
OUT.
NUTRIENT BALANCE STUDIES NOT
COMMONLY DONE.
WONDERFUL WORK FROM FORTIES,
50's, 60s, IN THE COME COME
AREA I CAN'T IMAGINE PUTTING A
BABY ON A BALANCE BED.
ASSESSING RELIES ON MARKERS THAT
DO NOT REFLECT WHOLE BODY
STATUS, SERUM MINERALS, SERUM
CALCIUM IS NOT A GOOD MARKER,
PROBLEMATIC IF WE WANT TO ASK
HOW DOES BIOACTIVE AFFECT BONE
FELT TO GET BONE DENSEY
MEASUREMENTS.
ALL THESE ARE VERY LIMITED.
EVEN WHEN WE CAN USE THE TYPE OF
DATA, IT'S EXTRAORDINARILY HARD
ESPECIALLY IN UNITED STATES FOR
INFANTS IN RESEARCH REQUIRING
SEQUENTIAL PHLEBOTOMY, DIFFICULT
TO OBTAIN CURRENTLY.
AREAS NEED CONSIDERATION, NO
DATA ASSESSING COST-BENEFIT.
NOW, WHEN WE TALK ABOUT
COST-BENEFIT, PEOPLE WOULD RAISE
EYEBROWS, I WANT THE BEST.
THAT'S NOT REALISTIC.
IF ADDING A BIOACTIVE, WHICH MAY
OR MAY NOT HAVE BENEFITS
INCREASES COST OF INFANT FORMULA
BY 50%, IT HAS HUGE CONSEQUENCES
FOR AVAILABILITY OF GOVERNMENT
AND SOCIETY, NOT TO MENTION
COUNTRIES ACROSS THE WORLD WHO
USE THOSE.
WE CAN'T SIMPLY SAY ESPECIALLY
GIVEN DATA THAT COST DOESN'T
MATTER.
WE HAVE TO CONSIDER WHETHER OR
NOT HOW WE PERCEIVE THE
COST/BENEFIT RELATIONSHIP WHEN
WE TALK ABOUT ADDING NOVEL
COMPONENTS.
DIFFERENT INFANT FORMULA
COMPANIES IN THE UNITED STATES
AND ELSEWHERE OFTEN MARKET,
DIFFERENT BIOACTIVES, WE DON'T
KNOW HOW THEY RELATE, WHAT
HAPPENS IF ONE COMPANY USING
ONE, ANOTHER COMPANY USES
ANOTHER BIOACTIVE, FAMILIES MAY
GO BACK AND FORTH BETWEEN THEM,
THESE FORMULAS, ET CETERA, THE
INTERACTION IS INTRODUCED BY
DIFFERENT CONDITIONS, DIFFERENT
AREAS HAVE TO BE CONSIDERED.
IT WOULD BE AN UNDERSTATEMENT TO
SAY RESEARCH WE HAVE DONE ON
BIOACTIVES HAT NOT BEEN
PRESENTED IN A WAY THAT'S USEFUL
TO CONSUMERS OR PEDIATRICIANS.
WHAT DOES DATA MEAN.
AND NO ONE FIGURED OUT A GOOD
WAY TO DO THAT.
THEREFORE THAT'S LEFT A VOID
HARD TO FILL BY CORPORATIONS
THAT MARKET FORMULAS RATHER THAN
INDEPENDENT GROUPS.
MOST OF THE STUDIES, RELATIVELY
FEW CLINICAL OUTCOMES RELATED TO
INFECTION OR ALLERGY PREVENTION.
WE'VE MENTIONED THE ISSUE OF
INCOME AND SYMPTOMS INCLUDE
COLIC, IT GETS HARD TO LIMIT
COMMON SYMPTOMS SUCH AS COLIC OR
REFLUX FOR THAT MATTER TO
SPECIFIC COMPONENTS OF HUMAN
MILK OR FORMULA.
WE NEED TO DO OUR BEST WHEN WE
LOOK AT BIOACTIVES TO DO THAT.
I'M GOING TO MENTION HUMAN MILK
OLIGOSACCHARIDES.
OTHERS ARE SPOKEN ABOUT THESE.
THE PURPOSE IS NOT TO SAY
THERE'S ANYTHING THAT DOESN'T
SUGGEST OLIGOSACCHARIDES IN
HUMAN MILK ARE UNSAFE AND NOT
EFFECTIVE BUT TO LOOK AT SOME
LITERATURE AND POINT OUT HOW THE
CHALLENGES I'VE MENTIONED ARE
REFLECTED IN THE CURRENT
LITERATURE WE HAVE AND HOW WE
NEED MORE RESEARCH TO LOOK AT
THESE ITEMS.
I WON'T GO THROUGH DETAILS OF
THE OLIGOSACCHARIDES, DESCRIBED
HERE.
AGAIN, THERE'S A SMALL
LITERATURE OUT ABOUT THEM.
SO ONE STUDY DONE WAS PUBLISHED
IN 2015 AND 2016 USING EXCELLENT
STUDY DESIGN, SERVES AS CONTROL,
TWO LEVELS OF OLIGOSACCHARIDES,
TWO PRIME, CONTROL GROUP, THAT
GIVES A CHANCE TO LOOK AT ISSUES
MENTIONED IN THE GROUPS,
DIFFERENT LEVELS, AND DO A BEST
FED CONTROL GROUP, FOLLOWED FOR
UP TO FOUR MONTHS.
OUTCOMES SHOW BREASTFED INFANTS
AND EXPIRMTDAL FORMULA SHOWED
BIOCHEMICAL BENEFITS.
I'LL DEFER TO IMMUNOLOGIST TO
DISCUSS HOW POTENTIALLY
IMPORTANT THESE ARE IN TERMS OF
IMMUNOLOGICAL OUTCOMES BUT SOME
OF THE ONES FOUND WERE SHOWN
THERE AND CERTAINLY MAY HAVE
SUBSTANTIAL BENEFITS, AGAIN, I
DEFER TO IMMUNOLOGISTS ON THAT.
I WILL POINT OUT HOWEVER AS THE
STUDY DID NOT REALLY LOOK AT
FUNCTIONAL OUTCOMES, DID NOT DO
LONG-TERM EVALUATIONS OF SAFETY
OR BENEFIT, DID NOT LOOK AT
INFANTS HIGH RISK OF INFECTION,
AND THEY SUGGEST POSSIBLE
BENEFITS BUT MORE DATA ARE
NEEDED.
SECOND SIMILAR STUDY CONDUCTED
IN EUROPE LOOKED AT CONTROL
FORMULA, HUMAN OLIGOSACCHARIDE,
NO CONTROL GROUP, MORBIDITY
ASSESSMENT BY PARENT REPORT, NOT
PHYSICAL EXAMINATION OR
PHYSICIAN REPORT WHICH IS A
LIMITATION, BOTH GROUPS GREW
WELL.
FUNCTIONAL OUTCOMES ARE
IMPORTANT.
TEST FORMULA GROUP REPORTED LESS
BRONCHITIS, LESS ANTI-PYRET AND
ANTIBIOTIC USE.
THIS IS THE TYPE OF DATA WE NEED
AND THERE NEEDS TO BE A
BREASTFED CONTROL GROUP THAT'S
DONE IN THESE STUDIES.
SO CONCLUSION FROM MY
PERSPECTIVE CLINICAL
PERSPECTIVES WE HAVE A LOT OF
EXCITING DATA BUT WE HAVE SMALL
STUDIES AND LIMITED LONG-TERM
OUTCOMES AND NEED FOR FURTHER
RESEARCH.
THIS IS A MODEL FOR WHERE WE
NEED TO GO.
AND I MENTION THE COST/BENEFIT,
AND NEED TO MENTION ISSUE OF
EQUITY.
EQUITY MUST BE CONSIDERED AS WE
TALK ABOUT INTRODUCING
COMPONENTS OF THE FORMULA.
IF NOVEL PRODUCTS INCLUDE
BIOACTIVES LEAD TO IMPROVED
CLINICAL OUTCOME SHOULD THEY BE
GIVEN TO ALL VULNERABLE INFANTS
INCLUDING THOSE WHO ARE PART OF
THE WORK PROGRAM?
SOME WIC FORMULAS PROVIDE
MARKETED BIOACTIVES, THEY DO
INCREASE COST COMPONENT BUT IF
SOMETHING IS BENEFICIAL ENOUGH
TO PUT IT IN FORMULA IT SHOULD
NOT BE MADE AVAILABLE TO
EVERYONE, SHOULD THEY BE
PERMITTED WITHOUT THE MOM THERE?
AND ISSUE DO WE NEED TO RETHINK
INFANT FORMULA ACT, WHAT LEVELS
DO WE NEED TO GO, INFANT FORMULA
ACT IS IMPORTANT, IT WAS
CONGRESSIONAL, NOT A PURE FDA
GUIDANCE.
DO WE NEED TO REGULATE THESE VIA
CONGRESSIONAL GUIDANCE OR
STRICTLY BY THE FDA?
I WELCOME THE FDA INPUT AND
THOUGHTS.
WE NEED TO CONSIDER SOURCING AND
CONTAMINATION, ENVIRONMENTAL
ISSUES, MISSING CHARACTERISTICS,
GOES BEYOND BASIC SCIENCE WHAT
IT MEANS TO INTRODUCE A
BIOACTIVE INTO AN INFANT FORMULA
AND RISKS ASSOCIATED WITH RISK
AND PREMATURE OR
IMMUNOCOMPROMISED INFANTS.
I WANT TO FOCUS A COUPLE MINUTES
ON THE GOAL OF CLOSER OR CLOSEST
TO MOTHER'S MILK, IS IS IT A
MEANINGFUL GOAL?
I WOULD ARGUE IT IS NOT.
WE THINK ABOUT ADDING BIOACTIVES
INTO FORMULA WE SHOULD THINK
ABOUT MAKING THE INFANT FORMULA
THE BEST IT CAN BE, THAT WE
CANNOT BE CLOSE TO MOTHER'S MILK
WHICH USING COMPONENTS SHOWN TO
BE BENEFICIAL FROM MOTHER'S
MILK, RECOGNIZING IT'S A
DIFFERENT PROPERTY, AND
MARKETING MAY CONFUSE FAMILIES
TO BELIEVE WHAT WE'RE DOING IS
MAKING AN INFANT FORMULA IS OF
THAT IS THE SAME AS HUMAN MILK,
IT WILL ALWAYS BE DIFFERENT IN
NUTRIENT CONTENT.
FOR EXAMPLE THE ACT REQUIRES
MORE CALCIUM THAN IN HUMAN MILK
, CHEMICAL COMPOSITION IS
DIFFERENT, PROTEINS WILL ALWAYS
HAVE SOME DIFFERENCE IN IT.
WE TALKED ABOUT SOME OF THE
OTHER ISSUES THAT ARE LISTED
HERE.
AGAIN, THE KEY IS FOCUS ON THE
UNDERSTANDING WHAT IT ACTUALLY
MEANS TO PUT THE BIOACTIVE IN
THE COMPONENT.
AGAIN, THIS IS A MARKETING
TERM, CLINICAL OUTCOME IS NOT
COMPOSITION THAT MATTERS, AND WE
MUST IDENTIFY THOSE.
I WOULD ENCOURAGE US TO NOT
ALLOW THESE OR PERMIT THESE
TERMS TO BE USED IN ADVERTISING
AS IT CAN BE MISUNDERSTOOD BY
THE PUBLIC AND VIOLATES SPIRIT
IF NOT WORDING OF W.H.O.
GUIDANCE ON INFANT FORMULA
MARKETING.
WITH ACCEPTANCE AND USE OF DATA,
ANY FINDING MUST BE PRESENTED IN
A FASHION ACCESSIBLE TO CONSUMER
AND CAREGIVER, WE NEED TO LIMIT
USE OF POORLY DEFINED TERMS,
DICHOTOMOUS EVALUATION OF BREAST
OFFICERS US FORMULA FED IS NOT
REALISTIC.
AND WE NEED TO CONSIDER EFFECT
OF BIOACTIVES IN OLDER INFANTS,
THERE'S MIXED DIET, COMPLEX
MEDICAL CONDITIONS AS WELL.
WE NEED TO CONSIDER TERMS NOT
HELPFUL AND NOT USE THEM.
WE NEED LONG-TERM RESEARCH AS
NOTED WITH BIOACTIVES.
WE NEED TO CONSIDER EFFECTS OF
COMPLEX FEEDING PATTERNS AND
REALISTIC FEEDING PATTERNS,
RESEARCH FUNDING NEEDS TO BE
LONG TERM.
AND THE LAST ISSUE, I WILL POINT
OUT THE PIPELINE OF RESEARCHERS
IS EXTREMELY LIMITED NOW.
WE NEED TO BE ENCOURAGING AT ALL
LEVELS RESEARCH INTEREST IN THIS
TOPIC AMONG ALL SCIENCES,
INCLUDING PEDIATRICIANS.
THANK YOU.
>> THANK YOU, RECEIVE.
MAYBE SHELLEY, CAN YOU COME ON?
UNFORTUNATELY BECAUSE WE'RE
RUNNING SHORT ON TIME THERE'S A
LOT OF INTERESTING QUESTIONS AND
DISCUSSION GOING ON IN THE CHAT
BOX AND E-MAIL.
UNFORTUNATELY THE BEST WAY TO
TACKLE A LOT OF THEM IS
HOPEFULLY THROUGH DISCUSSION AT
THE END OF TODAY OR POSSIBLY
FRIDAY.
AND I HOPE BOTH OF YOU CAN BE
ACTIVE PARTICIPANTS ON THE
DISCUSSION.
I WON'T -- I'LL HOLD OFF ON
ASKING QUESTIONS.
STEVE, YOU MENTIONED THE CONCEPT
OF LONGER STUDY WHEN WE EVALUATE
THESE THINGS.
WHAT IS YOUR THOUGHT, WHAT YOU
CONSIDER LONG-TERM STUDY, WHAT
ARE YOU LOOKING FOR AND SHOULD
THAT BE SUITED TOWARD PARTICULAR
BIOACTIVE COMPONENT IN TERMS OF
POTENTIAL FUNCTION OR DO YOU
THINK THERE ARE SOME LONG-TERM
STUDIES, QUOTE/UNQUOTE, THAT
COULD APPLY TO MOST OF THEM,
MAYBE I'LL JUST QUICKLY ASK YOU
THAT ONE.
>> SURE.
FROM A SAFETY PERSPECTIVE I
THINK WE NEED TO BE ASSURED THAT
THE ADDITION OF THE COMPONENT IS
SAFE THROUGHOUT CHILDHOOD.
IF YOU TAKE ONE OF THE EARLIEST
BIOACTIVES, THAT WAS ADDED, DHA,
A NUMBER OF YEARS AGO, WE NOW
HAVE -- 15, 20 YEARS EXPERIENCE,
IT WAS THE OPPORTUNITY TO GO
BACK AND TAKE A LOOK AT SOME
LONG-TERM HEALTH OUTCOMES,
RELATED TO DHA, I THINK THOSE
ARE THINGS -- WE NEED TO ENSURE
WE'RE BEING SAFE BEYOND THE
INFANCY AND INITIAL EARLY
CHILDHOOD EXPERIENCE AND I THINK
WE NEED POST MARKETING
SURVEILLANCE, AS YOU KNOW, THE
GUIDANCE FROM INSTITUTE OF
MEDICINE TALKED ABOUT POST
MARKETING SURVEILLANCE OF
BIOACTIVES, AND I THINK THIS,
PERHAPS MORE NEEDS TO BE DONE.
>> THANK YOU.
AND BEFORE I LET BOTH OF YOU GO
I DO HAVE ONE OTHER QUICK
QUESTION FOR BOTH OF YOU.
THAT IS, WHEN WE THINK ABOUT
HUMAN MILK USING HUMAN MILK AS
REFERENCE, WE OFTEN TEND TO
FOCUS ON ONE PARTICULAR
BIOACTIVE INGREDIENT INCLUDING
HMOs, RIGHT?
AND SO IN TERMS OF THINKING
ABOUT USING HUMAN MILK WITH
RESPECT TO APPLY WHATEVER CON
TATEIVE MEASURES IN ONE
PARTICULAR BIOACTIVE COMPONENT,
USUALLY TYPICALLY MIXED WITH
OTHER RELATED COMPONENTS HOW DO
YOU THINK WE SHOULD TAKE THAT,
THE FACT HUMAN MILK IS A VERY
COMPLEX BIOFLUID AND HAVE WE CAN
APPLY TO SAY A SINGLE INGREDIENT
IN TERMS OF RELATIONSHIP,
QUANTITATIVE RELATIONSHIP
BETWEEN WHAT'S IN HUMAN MILK
VERSUS A SINGLE INGREDIENT FOR
INFANT FORMULA, EITHER ONE OF
YOU COULD CHIME?
>> YOU CAN TAKE THAT, SHELLEY.
>> THANKS A LOT.
THAT'S THE WHOLE IDEA BEHIND THE
BEGIN PROJECT.
YOU KNOW, HAVING STRUGGLED ON
WRITING THOSE REPORTS I THINK
WE'RE IN THE DISCOVERY PHASE.
I THINK AT THIS PHASE WE ADD
SINGLE INGREDIENTS AND THEN WE
CHANGE AS THE KNOWLEDGE EVOLVES.
I THINK THAT'S HOW THIS WORKS.
I DON'T THINK IT SHOULD PRECLUDE
ADDING SINGLE INGREDIENTS IF WE
HAVE EVIDENCE TO BELIEVE THEY
ARE BENEFICIAL.
>> OKAY.
THANK YOU BOTH.
PLEASE CHIME IN AND ALL UPCOMING
DISCUSSIONS, YOU HAVE VALUABLE
INSIGHTS.
WITH THAT I BELIEVE WE CAN TAKE
A BREAK.
ASHLEY, DO YOU WANT TO SET TIME
IN TERMS OF WHEN YOU WANT
EVERYONE BACK FOR THE NEXT
SESSION?
YES, THANK YOU.
THANKS TO THE SPEAKERS.
YES, LET'S DO A 10-MINUTE BREAK.
WE HAVE A GOOD AMOUNT OF TIME
BUILT IN AT THE END OF THE DAY
SO I THINK EVERYONE COULD USE A
10-MINUTE BREAK, THE TIMER WILL
BE SET SO WE'LL COME BACK AROUND
2:10 EASTERN STANDARD TIME.
THANK YOU.
>> WELCOME TO SESSION 3,
CONSIDERATIONS OF INTERACTIONS
BETWEEN BIOACTIVE INGREDIENTS
DURING PROCESSING OR VIA THE
MATRIX.
I'M DR. ASSAD, CO-MODERATING
WITH LIEUTENANT KIMBERLY GIBBS
FROM NATIONAL INSTITUTES OF
HEALTH.
THIS SESSION WILL COVER HOW THE
MATRIX FOR PROCESSING AFFECTS
FUNCTION OR SAFETY OF BIOACTIVE
INGREDIENTS.
WE WILL BEGIN WITH A BRIEF
INTRODUCTION OF OUR SPEAKERS IN
PRESENTATION ORDER, AS DREW
MENTION THEIR BIOGRAPHIES ARE ON
THE WEBSITE, WE ENCOURAGE YOU TO
SUBMIT QUESTIONS AND QUESTIONS
TO THE WORKSHOP E-MAIL ADDRESS,
THAT ASHLEY PROVIDED EARLIER
TODAY.
OUR FIRST SPEAKER IS DR. DAVID
SELA, DEPARTMENT OF FOOD
SCIENCE, UNIVERSITY OF
MASSACHUSETTS, DEPARTMENT OF
MICROBIOLOGY AND PHYSIOLOGICAL
SYSTEMS AT UMass, SPEAKING ON
TECHNICAL INTERACTION WITH
SPECIAL EMPHASIS ON MICROBIOME.
SECOND SPEAKER IS DR. KASPER
HETTINGA, ASSOCIATE PROFESSOR IN
DAIRY SCIENCE AND TECHNOLOGY AND
WILL BE SPEAKING ON THE EFFECTS
OF PROCESSING ON MILK PROTEIN.
>> PLEASE JOIN ME IN WELCOMING
DR. SELA.
PLEASE SHARE YOUR SLIDES.
>> WONDERFUL.
I ASSUME YOU CAN HEAR ME JUST
FINE.
>> YES, SIR.
>> THANK YOU VERY MUCH FOR
ORGANIZING THIS AND PREVIOUS
SPEAKERS.
IT WAS ILLUMINATING.
I'M LOOKING FORWARD TO
FURTHERING THE DISCUSSION AND
GETTING INPUT.
I WAS ASKED TO PRESENT, I'M
PROUD TO DO SO.
I'LL TALK ABOUT MY EXPERTISE AND
HOW THIS RELATES TO STORAGE OF
FORMULA PERTAINS TO MICROBIOME
ACTIVE INGREDIENTS THROUGH
STORAGE, PROCESSING BEFORE THAT,
AND DISTRIBUTION.
WE'RE TALKING ABOUT THE LAST 12
MONTHS, THESE ARE MY INTERESTS,
ONE OF NOTE TO MENTION HERE,
THANK YOU SO MUCH FOR HMO
DONATIONS, WE APPRECIATE THEM.
THAT'S A SHOT OF MY CAMPUS WHERE
MY TEAM IS WORKING.
WHAT WE DO, WE WORK TO
UNDERSTAND STRUCTURE OF
FUNCTIONAL RELATIONSHIPS BETWEEN
HUMAN MILK COMPONENTS IN THE GUT
MICROBIOTA AS WELL AS HAVING
FUNDAMENTAL PERSPECTIVE OF
WHAT'S GOING ON.
WE'RE INFORMING CLINICAL
APPROACH, WE'RE NOT CLINICAL
SCIENTISTS IN THE LABORATORY.
IT'S A VERY INTERESTING TIME WE
FIND OURSELVES IN, OVER THE LAST
YEAR AND A HALF OR SO I THINK WE
HAVE COLLECTIVELY THOUGHT ABOUT
OUR JOBS, ROLES, RELATIONSHIPS
WITH WORK, MAYBE IDENTITY WITH
WORK TOO.
AND SO EVEN THOUGH I TALK TO MY
STUDENTS ALL THE TIME, IT
DOESN'T MAKE A DIFFERENCE WHAT
NAME IS ON THE DEGREE, WHAT
DEPARTMENT, IT'S WHAT YOU DO
WITH IT.
I HAPPEN TO BE DEPARTMENT OF
PRE-SCIENCE, UMass, I'M A
SCIENTIST, BIOLOGIST, NUTRITION
SCIENTIST, WE IDENTIFY WITH
DEPARTMENT OF FOOD SCIENCE, SO
THIS IS MY EIGHTH YEAR, WE'RE
PAYING ATTENTION TO WHAT WE CAN
DO TO ADVANCE THE CURRENCY OF
NUTRITION, THE WHOLE CULTURE HAS
BEEN ENABLING FOR US TO FURTHER
OUR RESEARCH AND TRANSLATION
MISSION, TO GUIDE INNOVATION IN
INFANT NUTRITION.
I TEND TO BE ASKED TO SIT ON
DISSERTATION COMMITTEES AND ORAL
EXAMS AND A LOT OF NUTRITION
SITES, IN ORAL EXAMS I TEND TO
ASK MORE NAIVE QUESTIONS FROM
NUTRITION STANDPOINT.
THE FORMULATIONS AND PROCESSING
TENDS TO BE MUCH MORE OF A
RUDIMENTARY UNDERSTANDING FROM
MY PERSPECTIVE, THAT'S MY
BACKGROUND TOO.
WE HAVE KASPER COMING UP TALKING
ABOUT THE NITTY-GRITTY OF
FORMULATION AND PROCESSING.
OVER THE COURSE OF PREPARING
THIS TALK I CAME TO THE
REALIZATION WE PUT TEAMS
TOGETHER WITH FOLKS OF BUSINESS
BACKGROUNDS, MAYBE TRAINING WITH
SENIOR SCIENTISTS, I WAS ABLE TO
ASK NAIVE QUESTIONS ABOUT
WHETHER WE ARE IN THE FIELD AND
HOPEFULLY COULD INSPIRE SOME
CONVERSATION DISCUSSION MOVING
FORWARD ON THIS TOPIC,
REGARDLESS.
I'M HAPPY TO BE HERE, PART OF
THE CONVERSATION.
THIS IS TREMENDOUSLY IMPORTANT
WORK WE'RE DOING RIGHT NOW.
YOU HEARD ME SPEAK BEFORE ON
THIS TOPIC, PASSIONATE ABOUT
ENGAGEMENTS BETWEEN ACADEMICS,
INDUSTRY, GOVERNMENT, REGULATORS
INCLUDED WITHIN THAT,
CLINICIANS, AND OF COURSE FOR
THE PURPOSES FOR ADVANCING
INFANT MATERNAL FAMILY HEALTH.
THAT'S REALLY WHERE IT STARTS
AND STOPS.
MEGAN AND OTHER PEOPLE WERE
TALKING ABOUT IT.
WE CAN LEARN ALL THERE IS ABOUT
MICROBIOME BUT WE'RE PASSIONATE
ABOUT ADVANCING INFANT HEALTH.
THAT'S GREAT TO BE SURROUNDED BY
COMMUNITY THAT BELIEVES IN THIS
WHOLEHEARTEDLY.
>> I HATE TO INTERRUPT.
WE COULDN'T DEGREE MORE.
ARE YOU IN PRESENT -- COULDN'T
AGREE MORE.
ARE YOU IN PRESENTER MODE?
WE'RE SEEING SLIDES ON OUR VIEW.
>> I'M IN SOME SORT OF MODE.
IF I'M IN PRESENTER MODE IT
MIGHT MESS THINGS UP.
MY SYSTEM IS WONKY.
>> WE CAN SEE EVERYTHING.
I JUST WANTED TO LET YOU KNOW.
THANKS.
>> APPRECIATE IT, DREW.
MOVING FORWARD HERE, OUR LAB
INVESTIGATES RECIPROCAL
INTERACTION BETWEEN HUMAN MILK
STRUCTURE AND PROPERTIES OF
INFANT GUT MICROBIOME, WE'VE
TALKED ABOUT THIS QUITE OFTEN,
HOW WE ARE A BIFF LAB, WE'RE
AGNOSTIC TO ACTUAL TAXA INVOLVED
WITH OPERATIONS WITHIN THE
INFANT.
IF IT HAPPENS TO BE
BIFIDOBACTERIA, THAT'S
FANTASTIC.
WE HAVE EXPERTISE AND
EXPERIENCE.
BUT THAT MAY NOT NECESSARILY BE
THE CASE ACROSS HUMANITY.
WE'RE LOOKING FROM A MICROBIOME
STANDPOINT WITH EMPHASIS ON
BIFIDOBACTERIA.
WE LOOK WITH SYNTROPHIC
INTERACTIONS, AND HOW THEY
PROCEED AS ONE MICROBE CONSUMES
ANOTHER AND IMPACTS INFANT
PHYSIOLOGY OR NEAR NEIGHBOR
WITHIN THE MICROBIOME SEPARATED
BY SHORT DISTANCES, APPLY SYSTEM
LEVEL APPROACHES.
THIS GETS INTO THE BUSINESS OF
THE PHILOSOPHICAL, WHAT IS
HUMAN, WHAT IS MICROBIAL AND WHY
DOES IT MATTER, ONE EXPERIENCE
FOR THE INDIVIDUAL, INFANT DOES
NOT HAVE THE ABILITY TO
COMMUNICATE THE EXPERIENCE TO
THE SAME DEGREE THAT WE DO
PERHAPS.
BUT IT IS ONE CONTINUUM.
WE STUDY INTERACTION BETWEEN
GROUPS OF NEUTRAL AND ACIDIC
HMO, THIS COULD BE INDIVIDUAL OR
GROUPS, AND HOW THAT IMPACTS
STRAINS, SAME WITH EMPHASIS IN
UREA AS WELL AS OTHER SOURCES
TOO.
WHERE WE GET EXCITED ABOUT THIS
STUFF IS HOW DO THEY ALL
INTERACT TOGETHER, IN AN IN
VITRO SYSTEM HOW WE EXPLORE
THESE BUT WHEN WE WORK WITH
PARTNERS, IN VIVO SYSTEMS, ALL
THIS RAISES THE QUESTION IF
WE'RE DOING THIS WORK, THIS
BIOLOGY AT THE BENCH LOOKING TO
GUIDE INNOVATIONS AND FORMULAS
HOW, IF WE'RE ABLE TO DICTATE
WHAT WOULD BE A SKILLFUL
SELECTION, MILK
OLIGOSACCHARIDES, NON-PROTEIN
NITROGEN SOURCES OR OTHER
NITROGEN SOURCES, HOW DO THEY
INTERACT WITHIN THE MATRIX OF
CELLS?
HOW WOULD THAT INTERACT IN
PROCESSING AND INTERACT DURING
STORAGE AND DISTRIBUTION AND
THOSE CONSIDERATIONS AS WELL?
SO MILK CARBOHYDRATE COUPLED
WITH THE CELL SYSTEM, WE DID A
LOT OF WORK IN THAT.
THE MICROBIOME, I WON'T GET INTO
THIS FIGURE, GENERATED BY A GRAD
STUDENT, LOOKING AT MILK
OLIGOSACCHARIDES, HOW METABOLISM
IS COUPLED TO UREA METABOLISM.
BIG QUESTIONS WE HAVE HERE.
OVERARCHING, HOW DO BIOACTIVE
INGREDIENTS INTERACT WITHIN THE
INFANT AND HOW DO THEY INTERACT
IN PROCESSING, STORAGE,
DISTRIBUTION, AND I'VE LEARNED
TO ASK THESE QUESTIONS IN
CERTAIN ROOMS, AMONG CERTAIN
PEOPLE, WHO ARE TREMENDOUSLY
SKILLED AT SOLVING THESE
CHALLENGES.
SO YOU CAN READ THIS OFF
YOURSELF HERE.
THESE ARE THE BIG QUESTIONS THAT
WE HAVE FOR THIS PARTICULAR
SESSION.
APPRECIATE AGAIN CONTRIBUTING TO
IT.
HERE'S WORK NOT FROM OUR GROUP
BUT FROM LARS' GROUP AND ANOTHER
ONE, IT'S BEEN REPEATED, THESE
GENERAL OBSERVATIONS, AND OTHER
LABORATORIES AROUND THE WORLD.
HMOs ARE FAIRLY STABLE DURING
PASTEURIZATION, ALLOWS CURRENT
STRATEGY OF INCLUSION OF MILK
OLIGOSACCHARIDES WITHIN INFANT
FORMULATIONS, MILK FORMULATIONS
AND DISTRIBUTION, AND SO FORTH.
THAT INCLUDES CURRENT STRATEGIES
AND ENVISIONED FUTURE STRATEGIES
AS COST EFFECTIVENESS, ENABLES
THAT TO OCCUR WHEN WE HAVE WHAT
MAYBE I COULD LABEL MORE EXOTIC
HMOs BEING ADDED TO PROCESSES.
THE QUESTION WE HAVE AS A GROUP
BECAUSE IT'S SOMETHING WE STUDY
DIRECTLY, HOW WOULD THIS BE
IMPACTED BY ADDING PROBIOTICS
INTO THE MATRIX ITSELF?
THAT MAY NOT BE APPEALING IN ALL
INSTANCES, MOST INSTANCES, ANY
INSTANCES, BUT WHAT HAPPENS IN
FIVE OR TEN YEARS FROM NOW?
IT WAS HARD FIVE OR TEN YEARS
AGO WHAT THE LANDSCAPE WOULD
LOOK LIKE TODAY THIS VERY MOMENT
SO WHO ARE WE TO SAY WITH WHAT
WE LEARNED FROM PRECISION
NUTRITION APPROACHES,
FUNDAMENTAL UNDERSTANDING OF
THESE THINGS, THAT WE'RE NOT
GOING TO GRAVITATE TOWARDS THESE
SORT OF INTERVENTIONS.
I DON'T KNOW THIS.
SO, I WORK WITH A PERSON IN MY
DEPARTMENT, WHO IS AN EXPERT IN
EMULSION TECHNOLOGY, FOR
MICROENCAPSULATION OF
PROBIOTICS.
AND SO THIS SORT OF THING HAS
BEEN INNOVATED IN THE PAST FOR
STABILITY WITHIN FOOD MATRICES
TO ENCAPSULATE MICROBES FOR
TAMPA -- STABILITY.
WHAT ABOUT MAINTAINING SPATIAL
SEGREGATION BETWEEN MICROBIAL
ENZYMES?
AND THEIR SUBSTRATES THAT HAPPEN
TO BE INCORPORATED WITHIN THE
INFANT FORMULA ITSELF?
WE TALK ABOUT THAT FROM ACADEMIC
STANDPOINT.
I'M SO EXCITED WE HAVE FOLKS
FROM INDUSTRY JOINING US RIGHT
NOW ON THIS CALL OR THIS
WORKSHOP.
THIS MAY NOT BE THE CURRENT
APPROACH BUT HERE IN ACADEMIA WE
GET ASKED THESE QUESTIONS, MIGHT
BE UNCOMFORTABLE BECAUSE THEY
MAY NOT BE FEASIBLE RIGHT NOW
BUT TOMORROW -- WE HAVE
DREAMERS, WE WANT TO BENEFIT
MATERNAL/INFANT HEALTH.
THIS IS A SCHEMATIC, A MORE
RECENT ARTICLE HERE, I THINK
THIS IS DR. JULIE CLEMENTS'
ARTICLE, PLAYED A MINOR ROLE,
VERY HAPPY TO BE WORKING WITH
YOU.
THIS IS INFORMED BY PHYSIOLOGY,
IF YOU'RE A DAIRY SCIENTIST
YOU'RE FAMILIAR WITH UREA
NITROGEN SALVAGING.
UREA SEE SECRETED IN LUMINA IS
CLEAVED BY BACTERIAL ENZYMES
WHICH AVAILS USABLE MITROGENOUS
IS PROJECTS, SUPPLIED BY UREA
CYCLE, THAT OCCURS IN THE LIVER,
WITHIN THE LUMEN OF THE
GASTROINTESTINAL TRACT AND INTO
CIRCULATION.
HUMAN MILK IS ONE AVENUE OF
INFANT NUTRITION HERE.
UREA ACCOUNTS FOR A LARGE
FRACTION OF TOTAL AND
NON-PROTEIN NITROGEN IN HUMAN
MILK.
RECENTLY UPDATED WHAT THERE IS
TO KNOW WITH -- DAVE DOS LED A
FANTASTIC CHAPTER, I VERY MUCH
ENCOURAGE YOU TO CHECK THAT OUT.
ANYWAY, WE'RE ACTIVELY TESTING
THIS HYPOTHESIS, CLEAVES THIS
UREA, AND PROVIDES USABLE
SUBSTRATES TO THOSE.
THIS IS A CUTE PICTURE THAT ONE
OF MY -- NOW SHE'S A POST DOC
AND BRIGHAM AND WOMEN'S, SHE
MADE A FEW YEARS AGO HERE.
I WON'T SPEND MUCH TIME ON
SCIENCE, THE RESULTS, WE'VE BEEN
TALKING ABOUT THIS FOR A FEW
YEARS NOW, WE HAVE EVIDENCE B
INFANTIS RECYCLES, AND THAT'S
FANTASTIC, BASIS FOR THE WORK
WE'RE DOING NOW, PROUD TO
PARTNER WITH NICHD ON THIS
MOVING FORWARD.
SO IF THIS IS AN ESSENTIAL
PROCESS, MAYBE NOT THE MAIN WAY
THAT AN INFANT IS ABLE TO
RECOVER, RECOUP NITROGEN,
THERE'S OF COURSE PROTEIN WITHIN
HUMAN MILK THAT FULFILLS INFANT
NEEDS EARLY IN DEVELOPMENT, AND
PROTEINS REMAINS RATHER CONSTANT
EVEN DESPITE MOTHER'S
NUTRITIONAL CHALLENGES, SO IS
THERE AN INSTANCE WHICH UREA IS
HELPFUL TO BE ADDED TO FORMULA?
THIS IS PRESENT, WE KNOW FROM
SHARON DONOVAN'S WORK, DEPENDS
ON FORMULA, SOURCE OF FORMULA.
IT'S BOVINE BASED TESTED BEFORE.
EXCRETED WASTE PRODUCT, I DON'T
KNOW HOW YOU AS A MARKETER SAY
LIKE WE'RE GOING TO ADD BACK
UREA, THAT SOUNDS FUNNY, BUT I'M
GOING TO LABEL MYSELF, A
NUTRITION SIGNIST, BIOLOGIST,
THAT'S FOR MARKETERS TO FIGURE
OUT.
THAT'S AN INTERESTING ASPECT.
IT DOES HAVE GRAS STATUS,
GENERALLY REGARDED SAFE.
IF THERE'S INSTANCES WE
DETERMINE HELPFUL TO ADD IT BACK
TO INFANT FORMULA, HOW WOULD THE
PHYSICAL AND CHEMICAL PRODUCTS
OF SUPPLEMENTATION CHANGE THE
Ph, BEYOND THINGS OF THAT
NATURE TOO.
SO THAT'S THE GENERAL, AND I'M
GOING TO SAY -- I'M NOT QUITE
SURE.
I'M RIGHT NOW WORKING ON THE
ADDING VALUE TO THIS CONCEPT,
ADDING EVIDENCE TO THIS CONCEPT,
WHETHER OR NOT IT'S SOMETHING TO
BE PURSUED IN A NUTRITIONAL
INTERVENTION.
WE HAVE ONE THING WE KNOW
ALREADY PRESENT IN INFANT
FORMULA, IN SOME INSTANCES UREA
IS PRESENT FOR BOVINE COMPONENT
CONCENTRATIONS THAT REALLY
APPROXIMATE WHAT WE FIND IN
HUMAN MILK BUT IN PLANT-BASED
FOODS, FORMULA, WHICH IS
SOMETHING THAT I REMEMBER SEEING
A STATISTICS A FEW YEARS AGO
PERHAPS IN THE LATE '90s, 25%
OF THE MARKET WAS DRIVEN BY
PLANT-BASED OR SOY-BASED
FORMULAS.
I CAN'T FIND THAT AGAIN.
I DON'T KNOW IF THAT'S
ENVISIONED OR IMAGINED BUT I'VE
SEEN INSTANCES SOY-BASED
FORMULAS DIMINISHED IN
ENTHUSIASM DUE TO CONCERNS ABOUT
PHYTO ESTROGENS, AND THAT MAKES
INTUITIVE SENSE HERE.
WE'RE SEEING RISE IN PLANT-BASED
NUTRITION, PLANT-BASED PRODUCTS,
PLANT-BASED FOODS IN THE U.S.
MARKET.
GLOBALLY AS WELL.
I'VE SEEN TONS OF GRAPHICS IN
THE LAST YEAR, OUR DEPARTMENT
HERE AT UMass AMHERST IS
FOCUSED IN THE DIRECTION LOOKING
TO INNOVATE IN PLANT-BASED
FOODS, SOMETHING WE'RE
INTERESTED IN INFANT FORMULA
PERSPECTIVE HERE.
PLANT-BASED MILKS ARE STABLE
PRODUCTS IN MANY U.S.
HOUSEHOLDS, PLANT-BASED MATRICES
MUST BE CONFERRED.
IF WE'RE INCREASING CONSUMER
DEMAND OF COURSE SPECIFIC
PROCESSING NEEDS WILL BE
INCREASED.
MAYBE THAT'S WHERE OUR WORK WITH
UREAS MAKES THE MOST IMPACT IF
IT'S IMPORTANT IN NUTRITIONAL
CONTEXT.
SO I'M GOING TO END OVER HERE,
TWO SLIDES, AND HOW DO WE KEEP
NEXT GENERATION SAFE AND STABLE?
I APPRECIATE THE TALK BEFORE,
RAISING COMPELLING PROVOCATIVE
POINTS THAT GOT ME THINKING
ABOUT A FEW THINGS CONSISTENT
WITH THINGS I WAS THINKING ABOUT
AS PREPARING THIS TALK, OVER THE
COURSE OF THE LAST FEW YEARS
TALKING IN THE LABORATORY, HOW
WILL INGREDIENTS HARVESTED FROM
CELLULAR PROCESSING AND STORAGE
CONSIDERATIONS, I HAVE A CHANCE
TO MEET WITH ALL KINDS OF SMART
FOLKS ON THIS WORKSHOP, EITHER
BACKSTAGE OR IN A BROADER WORLD,
AND SOME FOLKS HERE ARE
INTERESTED IN CELLULAR
AGRICULTURE, IN ORDER TO PROVIDE
INGREDIENTS TO GO INTO
PRODUCTION STREAMS.
HOW DOES THIS NEW WORLD IMPACT
STABILITY AND SAFETY?
I DON'T KNOW.
I RAISE THIS AS A POINT, I WOULD
LOVE TO LEARN.
CONSIDERATIONS FOR
PHYTOCHEMICALS, THAT ARE NOT
TYPICALLY SECRETED TO INCREASE
PERFORMANCE AND EFFECTIVENESS,
POLYPHENOLS, PHYTO CANNABINOIDS,
I'M NOT SUGGESTING WE TOSS IN
THC TOMORROW TO CURE COLIC BUT
THE QUESTION AS WE UNDERSTAND
PARAMETERS, LIMITATIONS AND
BOUNDARIES OF TOXICOLOGY, WE CAN
ASK THE QUESTION, AND NOT BE
SCARED OF ASKING IT.
IT'S JUST A QUESTION.
I DON'T THINK THAT'S GOING TO BE
THE THING WE'LL LEAD WITH BUT
MAYBE WE'LL START WITH
POLYPHENOLS.
WHAT PLANT BASED OLIGOSACCHARIDE
COULD PROMOTE IMPACT IN INFANT
GUT, SIMILAR TO WORK WE'RE DOING
RIGHT NOW TRYING TO UNDERSTAND
THE OVERLAP, VENN DIAGRAM OF
EFFECTIVENESS OF HUMAN MILK
OLIGOSACCHARIDES COMPARED TO
PLANT-BASED OLIGOSACCHARIDES.
AND DO WE NEED THEM TO BE THE
SAME SORT OF ACTIVITIES AND HOW
DO WE DEFINE ACTIVITIES?
OF WHAT ARE THE THRESHOLDS OF
EFFECTIVENESS THAT WE HAPPEN TO
BE CONCERNED WITH?
WHAT DO WE MEASURE?
THINGS LIKE MEGAN ASSAD ASKS,
WHAT IS IMPORTANT TO MEASURE IN
THE LABORATORY, FUNDAMENTAL
DISCOVERY PHASE, AND THEN OF
COURSE VERY IMPORTANTLY IN THE
CLINICAL PHASE.
I'LL END WITH THIS.
THE APPROPRIATE VIEW IS GOLD
STANDARD TO INFORM INFANT
FORMULATIONS, GREAT.
I THINK THAT'S PROBABLY STRONGER
LANGUAGE THAN MAYBE STEPHEN
WOULD APPRECIATE HERE BUT
REGARDLESS OF WHAT MAGNITUDE
THAT YOU'RE PLACING ON THIS,
WE'RE LOOKING AT WHAT'S THERE,
HOW IS THAT IMPACTING NUTRITION
FROM FUNDAMENTAL STANDPOINT
HERE?
AND THEN MOREOVER, IN WHAT
INSTANCE COULD THIS IF IT'S THE
ONLY GAME IN TOWN, APPROXIMATING
THIS, ARE WE ABLE TO VIEW INFANT
FORMULA AS A SEPARATE CATEGORY
OF SUBSTANCE, WHICH IT IS, OF
COURSE.
BUT WE OF COURSE HAVE OUR MENTAL
MODELS ABOUT THESE THINGS AND
THAT'S OKAY BECAUSE WE ARE
HUMANS AND THAT'S WHAT HUMANS DO
VERY WELL.
ALL RIGHT.
WITH THAT I WILL END MY TALK,
AND I DON'T KNOW IF I HAVE TIME
FOR QUESTIONS BUT I AM GOING TO
BE HERE ALL DAY TODAY AND ALL
DAY TOMORROW.
>> OKAY.
CAN EVERYONE SEE ME?
WONDERFUL.
OKAY.
THANK YOU SO MUCH, FOR THAT
PRESENTATION.
WE REALLY DON'T HAVE TIME FOR
QUESTIONS, WE'RE GOING TO HOLD
THOSE UNTIL THE END.
I'D LIKE TO INTRODUCE -- WELCOME
OUR NEXT SPEAKER, DR. HETTINGA
TO SHARE HIS SLIDES WHEN HE'S
READY.
>> WELCOME TO MY PRESENTATION ON
CHANGES TO IMMUNOLOGICALLY
ACTIVE NEW PROTEINS.
AFTER A NUMBER OF BIOLOGY
ORIENTED TALKS BEFORE ME I WILL
BE TALKING MORE LIKE OUR REAL
FOOD TECHNOLOGIST, THAT'S WHAT I
AM, I WILL TALK ABOUT HOW
PROCESSING CHANGES NEW PROTEINS
AND HOW THAT CHANGES ALSO
BIOACTIVES IN MILK.
SO AS A DISCLOSURE, FUNDING FOR
RESEARCH IS BASE OF MY
PRESENTATION, HAS BEEN FUNDED BY
A NUMBER OF DIFFERENT
ORGANIZATIONS AND I'M SCIENTIFIC
ADVISER TO TWO STARTUPS.
THEN FIRST I WANT TO GIVE AN
INTRODUCTION ABOUT WHAT
BIOACTIVE MILK PROTEINS ARE, AND
WHAT DOES PROCESSING DO TO MILK
PROTEINS, AND THEN I WILL LOOK
AT HOW INTERACTION AMONG
COMPONENTS MAY ACTUALLY
INFLUENCE FUNCTIONALITY OF THESE
MILK COMPONENTS.
IF WE LOOK AT THE BIOACTIVE MILK
PROTEINS, ALREADY EARLIER TODAY
IT WAS MADE CLEAR THAT MILK
PROTEINS PLAY A ROLE ON ONE HAND
IN NUTRITION BUT ARE ALSO MILK
PROTEINS THAT PLAY A ROLE IN
PROTECTION OF INFANT, BY BEING
ANTIBACTERIAL, IMMUNOMODULATORY,
AND THAT'S ACTUALLY A WORLDWIDE
RANGE OF DIFFERENT PROTEINS THAT
ARE RESPONSIBLE FOR THAT.
LACTOFERRINS ARE IMPORTANT,
HUNDREDS OF DIFFERENT PROTEINS
EXIST IN MILK AND WORK TOGETHER.
SOME OF THESE PROTEINS CAN BE
ISOLATED OUT OF BOVINE MILK, MAY
BE ADDED TO INFANT FORMULA.
BUT THEN THE QUESTION IS WHAT'S
HAPPENING IF YOU LOOK AT SUCH
BIOACTIVE PROTEINS, HIGHER
CONCENTRATION TO INFANT FORMULA,
BOTH DURING PROCESSING AND HOW
THAT CHANGES THE FUNCTIONALITY
OF SUCH PROTEINS.
AND THEN A QUESTION TO START
FROM, WHICH PROTEINS WOULD WE
LIKE TO ADD TO INFANT FORMULA TO
HAVE INFANT FORMULA BETTER
REPLICATE HUMAN MILK.
IF YOU LOOK AT DIFFERENCE
BETWEEN HUMAN AND BOVINE MILK WE
SEE A NUMBER OF PROTEINS
ENFORCED IN DEFENSE SYSTEM OF
MUCOSAL SECRETIONS ARE ALL
HIGHER IN HUMAN MILK THAN IN
BOVINE MILK.
WE KNOW THAT THE NEWBORN INFANT
IS NOT CAPABLE OF PRODUCING
THESE PROTEINS ALREADY FROM
BIRTH AT HIGH AMOUNT, SO
ACTUALLY HUMAN MILK IS PROVIDING
THOSE DEFENSE SYSTEM PROTEINS
THAT THE INFANT CANNOT YET
SUFFICIENTLY PRODUCE ITSELF.
SO SOME OF THESE PROTEINS CAN BE
ISOLATED OUT OF BOVINE MILK,
ADDED TO INFANT FORMULA, EXAMPLE
IS LACTOFERRIN NOW ADDED TO
INFANT FORMULAS.
BEFORE TALKING ABOUT WHAT INFANT
FORMULA PROCESSING COULD BE
DOING TO PROTEINS I WANT TO
BRIEFLY EXPLAIN THE DIFFERENT
STEPS OF FORMULA PRODUCTION AND
HOW THEY MAY IMPACT THE
CONVERSATION AND FUNCTIONALITY
OF INFANT FORMULA.
SO INGREDIENTS MIXED TOGETHER,
THEY ALREADY HAVE UNDERGONE HEAT
TREATMENTS TREATMENT, ALL
INDIVIDUAL INGREDIENTS ARE
ALREADY COMING FROM OTHER
PROCESSES OR HAVE UNDERGONE HEAT
TREATMENT, BUT ONE SHOULD MIX
THEM, HOMOGENIZE, HEAT IT AND
SPRAY DRY IT, THIS STEP AS WELL
AS HEATING STEPS THAT FOLLOW IT
CAN ALL IMPACT PROTEINS THAT ARE
PRESENT IN THE INFANT FORMULA.
SO TO FIRST LOOK SPECIFICALLY AT
HOMOGENIZATION, INTERACTION
BETWEEN FAT DROPLETS AND MILK
PROTEINS, IF WE HOMOGENIZE GET
MORE FAT DROPLETS, CASEIN AND
WHEY PRODUCTS, INCREASING
ACTIVITY SO ANTIBACTERIAL
ACTIVITY IS INCREASED.
THAT'S ONLY BASED ON VERY
LIMITED NUMBER OF VERY SMALL
STUDIES SO WHAT IT'S DOING OTHER
THAN THAT IS UNKNOWN.
ALSO WHEN IT COMES TO
IMMUNOLOGICAL IMPACT OF MILK
PROTEINS, THAT PRESENCE MAY
CHANGE THEIR DIGESTIVE BEHAVIOR
AND ALSO SUBSEQUENT IMMUNOLOGIC
RESPONSE TO MILK PROTEINS, MORE
COMPLICATED, ONLY CHANGING THE
LOCATION OF THE PROTEIN.
BUT ACTUALLY MOST RESEARCH
THAT'S BEEN DONE UP TO NOW IS
FOCUSING ON THE HEATING OF THE
MILK PROTEINS, IF WE HAVE A
NATIVE PROTEIN, HEAT, MAY PARTLY
UNFOLD, FIRST REACTION IS STILL
REVERSIBLE.
AT THAT POINT THERE MAY BE SOME
BONDS BROKEN, IF YOU COOL DOWN
MAY REVERSE.
IF WE HEAT HOT ENOUGH UNFOLDED
PROTEINS MAY START AGGREGATING,
IRREVERSIBLE PROCESS, GENERALLY
SPEAK FIGURE WE TALK ABOUT
ACTIVE PROTEIN USUALLY LOSE
BIOLOGIC ACTIVITY, FOR EXAMPLE
HEATING LACTOFERRIN, IT LOSES,
HEAT ENZYMES RELATIVE FOR
INFANTS ALSO LOSE THEIR
ENZYMATIC CAPABILITY AS SOON AS
WE GET PROTEIN AGGREGATION.
ALSO DIGESTION MAY BE CHANGED
DUE TO THIS PROTEIN AGGREGATION,
AND THAT MAY HAVE ALSO
NUTRITIONAL CONSEQUENCES BUT
THAT'S ALSO OUTSIDE THE SCOPE OF
THE LECTURE TODAY.
AND IF WE LOOK AT INFANT FORMULA
THERE'S A BUNCH OF REDUCING
SUGARS IN FORM OF LACTOSE
PRESENT, LACTOSE CAN CHEMICALLY
REACT TO PROTEIN, WHICH LACTOSE
WILL BIND TO THE PROTEIN AND
THIS CAN LOWER THE DIGESTIBILITY
OF PROTEINS, CAN INDUCING
INDUCE AGGREGATION AND LEAD TO
LOSS OF ACTIVITY.
OWN THOUGH WE MAY ISOLATE OUT OF
BOVINE MILK BY ACTIVE
COMPONENTS, DEPENDING ON THE
HEAT TREATMENT THAT IS BEING
DONE, UNFOLDING AGGREGATION CAN
LEAD TO LOSS OF FUNCTION,
CHANGES IN DIGESTION OF THESE
PROTEINS IN THE FINAL PRODUCT AS
CONSUMED BY THE INFANT.
MILK IS A VERY COMPLEX MATRIX OF
MANY PROTEINS.
ACTUALLY THE PICTURE I SHOWED ON
THE PREVIOUS SLIDE YOU COULD
INTERPRET FROM THE PERSPECTIVE
OF SINGLE PROTEIN, ACTUALLY ALL
THESE PROTEINS ARE INTERACTING
WITH EACH OTHER, SO YOU GET
AGGREGATED, THAT MAY ATTACH,
THAT CHANGES BOTH DIGESTION OF
MILK PROTEINS, ALSO IMMUNE
SYSTEM RESPONSE.
IF WHEY PROTEINS AGGREGATE THEY
ARE TAKEN UP IN THE INTESTINAL
TRACT IN A DIFFERENT WAY, ALSO
THE RESPONSE OF DENDRITIC CELLS
IS DIFFERENT FOR WHEY PROTEIN
AGGREGATE VERSUS MONOMERIC WHEY
PROTEIN.
AND THEN WE DID A NUMBER OF
STUDIES WHERE WE WANTED TO LOOK
SPECIFICALLY AT BIOACTIVE
PROTEINS.
AND WHAT WE SEE ACTUALLY FOR A
NUMBER OF BIOACTIVE PROTEINS
THAT 70 TO 75 DEGREES IS
TEMPERATURE MATURATION STARTS
HAPPENING.
WHAT WE SEE HERE ARE FOUR
PROTEINS AND LEVEL OF NATIVE
PROTEIN AFTER HEATING, WE SEE AS
SOON AS YOU REACH HIGHER
TEMPERATURE THAN 70 DEGREES
THESE PROTEINS START DECREASING
SO ALREADY MAY LOWER LEVEL OF
THESE PROTEINS, THIS IS
ANALYTICALLY HOW MUCH IS
PRESENT, MAY SURVIVE AS WIDELY
MORE INTENSE HEAT TREATMENT.
AND THEN WE ALSO LOOKED AT THE
GROWTH OF BACTERIA IN MILK.
BECAUSE NORMALLY THE PRESENCE OF
LACTOFERRIN AND IMMUNOGLOBULINS
MAY LIMIT GROWTH OF BACK
BACTERIA, AS SOON AS WE HEAT
BACTERIA GROW QUICKER, VERY
CLEAR NEGATIVE CORRELATION
BETWEEN LEVEL OF IMMUNE ACTIVE
PROTEINS AND GROWTH RATE OF
BACTERIA SO THAT MEANS AS SOON
AS THESE PROTEINS START
DECREASING IN THEIR LEVEL,
BACTERIA CAN MORE EASILY GROW IN
THAT MILK AS A WAY OF -- THAT'S
A KIND OF BIOMARKER THAT NOT
ONLY THE NATIVE STRUCTURE IS
DESTROYED BY THE HEATING BUT
ALSO FUNCTIONALITY OF THESE
PROTEINS IS HEATED, THAT ARE
HEATED IS DESTROYED
SIMULTANEOUSLY.
AND THIS IS ALSO VERY IMPORTANT
TO TAKE INTO ACCOUNT IF WE LOOK
AT BOVINE MILK THAT DIFFERENT
PROTEINS CAN INTERACT, I ALREADY
MENTIONED DIFFERENT WHEY
PROTEINS FORM AGGREGATION.
AFTER HEAT TREATMENT AND LIMITED
LEVEL OF AGGREGATION BUT IF
OTHER LEVELS ARE PRESENT, SHOWN
ON THE RIGHT, WE SEE AT THE
LOWER TEMPERATURE MUCH LARGER
AMOUNT OF AGGREGATE IS FORMED.
THAT MEANS LACTOFERRIN BEHAVES
DIFFERENTLY IF HEATED ALONG
VERSUS WHEN YOU HEAT IN A MILK
OR INFANT FORMULA MATRIX.
AND AN IMPORTANT REASON FOR THAT
IS THESE INTERACTIONS AMONG WHEY
PROTEINS.
IF ONE STARTS AGGREGATING, THE
PRESENCE OF OTHER MILK PROTEINS
IS REDUCING ACTIVITY OF THE
BIOACTIVE PROTEINS AFTER
HEATING.
AGGREGATING PROCESS AGGREGATES
MANY DIFFERENT PROTEINS THAT
AGGREGATE WITH EACH OTHER.
THEN WE ALSO LOOKED AT WHAT IS
HAPPENING ON A BIOCHEMICAL
LEVEL.
AND I WILL NOT GO INTO TOO MUCH
OF THE BIOCHEMISTRY HERE BECAUSE
IT'S QUITE A COMPLEX STORY, BUT
WHAT WE SEE AS SOON AS YOU GET
AGGREGATION, THE LACTOGLOBULIN
IS IN ABSENT IN HUMAN MILK, IT'S
A VERY REACTIVE PROTEIN, BINDING
TO OTHER BIOACTIVE PROTEIN,
THERE BY LEADING TO THE LOSS OF
FUNCTION OF THESE BIOACTIVE
PROTEINS.
WHAT WE SAW LACTOSE DIGEST,
LOSING ANTIBACTERIAL CAPACITY AS
SOON AS IT BINDS TO IT, THIS IS
QUITE AN IMPORTANT THING THAT'S
NOT ONLY TRUE FOR LACTOFERRIN,
SAME FOR OTHER BIOACTIVE MILK
PROTEINS AS SOON AS YOU PUT THAT
LACTOGLOBULIN IN YOUR MIXTURE
AND FORMULA IT'S THE MOST
ABUNDANT PROTEIN PRESENT, THIS
SINGLE PROTEIN DUE TO ITS
REACTIVENESS WILL BIND TO OTHER
BIOACTIVE PROTEINS AND IS THERE
BY CAUSING DAMAGE.
NOW, WE'RE ALSO STUDYING WHAT
CAN WE DO BECAUSE IF WE ARE LOW
PASTEURIZATION TO LEAD TO
INACTIVATION OF BIOACTIVE
PROTEINS, WE ALSO THINK ABOUT
OTHER TECHNOLOGIES THAT CAN HELP
IN INCREASING SAFETY OF A
PRODUCT, BUT AT THE SAME TIME
ALSO KEEPING BIOACTIVE
COMPONENTS INTACT.
WE'RE LOOKING INTO TECHNIQUES
THAT CAN BE ALONE, YOU CAN USE
COMBINATION OF TECHNIQUES AND
ALSO APPLY NON-THERMAL
TECHNIQUES TO STILL REACH A SAFE
PRODUCT.
AND WHAT WE SEE IF WE'RE DOING
THAT IS THE BACTERIAL GROWTH
RATE IN THE MILK IS MUCH REDUCED
COMPARED TO PASTEURIZATION
PROCESS, SO BY APPLYING
NON-THERMAL TECHNOLOGIES WE CAN
RETAIN THE FUNCTIONALITY OF THE
BIOACTIVE PROTEINS THAT ARE
PRESENT IN MILK.
REALLY KNOWING ON A LARGER SCALE
WHAT THE SAFETY ISSUES ARE
AROUND THESE NON-THERMAL
TECHNOLOGIES IS SOMETHING THAT
STILL NEEDS TO BE INVESTIGATED
MUCH FURTHER.
WITH THAT I REACHED THE END OF
MY PRESENTATION.
TAKEHOME MESSAGES, FIRST MILK
PROTEINS INTERACT WITH EACH
OTHER, AND ALSO WITH LACTOSE
DURING HEATING.
AND THAT IS REALLY LEADING TO
IMPORTANT DECREASE IN
BIOACTIVITY OF PROTEINS THAT MAY
BE ADDED.
WE KNOW SOME BIOACTIVE PROTEINS
THAT ARE ALSO NATIVELY PRESENT
IN BOVINE MILK ARE CURRENTLY
DESTROYED BY HOW WE PROCESS MILK
WITH REPEATED HEATING STEPS, WE
ARE MORE AND MORE REDUCING LEVEL
OF THESE PROTEINS.
OF COURSE, SOME OF THESE CAN BE
ADDED AS INGREDIENT, THERE ARE A
LOT OF HURDLES TO GET IN PROTEIN
THAT IS TAKEN OUT AS INGREDIENT,
TO HAVE A SAFE PRODUCT WHERE THE
FUNCTIONALITY IS RETAINED.
AND BIOACTIVE PROTEINS LOSE
FUNCTIONALITY DURING HEATING
MOSTLY DUE TO AGGREGATION, AND
THIS IS STUDIED IN LACTOFERRIN
ONLY, WE EXPECT SIMILAR
MECHANISMS PLAY A ROLE BUT IT
HAS NOT BEEN STUDIED IN DETAIL
YET.
SO WHAT MAY THE FUTURE BRING?
I THINK LOOKING INTO BOTH LOWER
HEAT LEVEL, ALSO ALTERNATIVE
PROCESSES MAY IMPROVE RETENTION
OF BIOACTIVE PROTEINS IN INFANT
FORMULA.
OF COURSE, IMPORTANT QUESTION TO
ANSWER IS WHAT IS SAFETY OF SUCH
ALTERNATIVE PROCESSES?
AND THAT CAN BE ADJUSTED
HEATING, IN THE END WE NEED TO
BE 100% SURE WE MAKE A SAFE
PRODUCT.
I ALSO THINK THAT COMBINING
STUDIES, ONE HAND HUMAN MILK,
OTHER HAND BOVINE MILK, PROSING
CAN LEAD TO FUNCTIONALITY, HOW
CAN WE BALANCE SAFE AND
FUNCTIONALITY?
ONE SPECIFIC ASPECT WHERE I
STARTED MY LECTURE WITH, IMPACT
OF HOMOGENIZATION, THIS IS
REALLY CHANGING THE STRUCTURE OF
MILK PROTEINS, STUDIED TO SUCH A
LIMITED EXTENT COMPARED TO OTHER
DAIRY PROCESS, SO WHAT IT IS
DOING TO THE SAFETY AND
FUNCTIONALITY OF INFANT FORMULA
IS FOR A LARGE PART STILL AN
UNKNOWN AREA.
THE WORK I PRESENTED TODAY IS
THE WORK OF A NUMBER OF
DIFFERENT Ph.D. AND MSC
STUDENTS IN COLLABORATION WITH
OTHER PEOPLE I WOULD LIKE TO
THANK FOR THEIR SUPPORT OF THIS
WORK AND WOULD LIKE TO THANK YOU
ALL FOR LISTENING AND BE MORE
THAN HAPPY TO ANSWER ANY
QUESTIONS YOU STILL HAVE ABOUT
THIS TOPIC.
>> THANK YOU.
WE APPRECIATE YOUR TIME.
THERE HAVE BEEN QUITE A FEW
QUESTIONS COMING IN.
WE'RE GOING TO TRANSITION BACK
TO DR. SELA, ASK A QUESTION TO
HIM AND THEN YOU, IF YOU'D LIKE
TO TAKE A REST.
DR. SELA, WE HAD A QUESTION IN
THE CHAT FROM THE E-MAIL.
WHAT IS YOUR VIEW OF OTHER
(INDISCERNIBLE) PRESENT IN HUMAN
MILK AS SUBSTRATE FOR INFANT
MILK MICROBES.
>> I APPRECIATE THE QUESTION.
WE HAVE SOME PRELIMINARY
EVIDENCE FOR VARIETY OF SMALL
AMINES AND POLY AMINES, HOW
THOSE ARE UTILIZED AS SUBSTRATES
BY MEMBERS OF INFANT GUT
MICROBIOME, WE'RE INTERESTING AS
A GENERAL SOURCE, THEY ARE
BROKEN DOWN TO AMMONIA, GET USED
IN ANABOLIC INTERACTIONS,
REACTIONS RATHER.
BUT ALSO COULD BE ACTING AS
SIGNALING MOLECULES, DEPENDING
ON DIFFERENT TYPE OF MOLECULE
THAT'S ENCOUNTERED BY THE
MICROBE, THEY COULD INITIATE
CASCADE IN WHICH A PHYSIOLOGICAL
PROCESS IS INITIATED OR PROGRAM
IS INITIATED TOO SO QUESTIONS
WE'RE REALLY INTERESTED IN
UNDERSTANDING TOO.
WE'RE EXCITED ABOUT
UNDERSTANDING INTERACTION
BETWEEN NITROGEN PRESENT IN GUT
OR SECRETED BY INFANT AND HOW IT
IMPACTS MICROBIOME AND INFANT
PHYSIOLOGY.
>> THANK YOU FOR ANSWERING THAT
QUESTION.
WE HAVE A QUESTION FOR YOU, DR.
HETTINGA, INTERACTIONS WITH
BIOACTIVES COMPARED TO BOVINE
MILK.
>> THAT'S A GOOD QUESTION.
WHAT WE DO SEE IS THAT THE
EFFECT OF HEATING OF HUMAN MILK
LEADS TO LOWER LOSS OF
FUNCTIONALITY, THAN WE SEE FOR
BOVINE MILK SO I ACTUALLY
EXPECTED THE PRESENCE OF --
THAT'S REASON WHY DAMAGE TO
FUNCTIONALITY HAPPENS BUT HARD
TO PROVE THAT BECAUSE STUDY
INTERACTION OF BLG WITH A LOT OF
INDIVIDUAL PROTEINS, YEAH,
REQUIRES A LOT OF TIME AND A LOT
OF EFFORT FOR EACH PROTEIN
SEPARATELY, NOT EASY TO PROVE
BLG IS THE REAL UNDERLYING
REASON HERE.
>> THANK YOU.
WONDERFUL.
DUE TO TIME, I WANT TO THANK OUR
WONDERFUL SPEAKERS AGAIN, AND
TRANSITION BACK TO ASHLEY, DR.
VARGAS, FOR THE NEXT AGENDA
ITEM.
>> THANKS AGAIN TO ALL OUR
SPEAKERS.
THIS IS THE PRE-WARNING, WE'RE
GOING TO ASK YOU COME BACK ON
VIDEO SHORTLY.
SO WE ARE MOVING NOW TO OUR Q&A
SESSION, WE'VE ADDED A
MODERATOR, TO FILL IN QUESTIONS
WE DIDN'T ANSWER IN SESSION 2.
WITHOUT FURTHER ADO I WILL TURN
IT OVER TO LEAD US OFF.
>> THANK YOU.
I WANT TO THANK THE SPEAKERS FOR
THESE FANTASTIC PRESENTATIONS.
WE HAVE QUITE A NUMBER OF
QUESTIONS, GENERAL QUESTIONS,
ALSO SOME FOR SPECIFIC SPEAKERS.
I'M NANCY POTISCHMAN, FROM NIH,
OFFERS OF DIETARY SUPPLEMENTS,
AND I LOOK AT THE RISKS AND
BENEFITS RELATED TO DIETARY
SUPPLEMENTS.
I'M HAPPY TO BE PART OF THE
PLANNING COMMITTEE.
ROBIN?
>> YES, THANKS SO MUCH.
I'M ROBIN McKINNON, CFSAN, I
WAS FORMERLY AT THE NIH FOR A
DECADE.
AND SO LOOKING FORWARD TO
MODERATING THIS GENERAL
QUESTION-AND-ANSWER SESSION WITH
DR. POTISCHMAN.
WE ASKED DR. KONAKO TO COME
BACK, THERE ARE A NUMBER OF
QUESTIONS, PARTICULARLY IN THE
SECOND SESSION, THAT WERE COMING
THROUGH.
I'LL INVITE HIM TO INTRODUCE
HIMSELF IN JUST A SECOND.
JUST TO NOTE THAT UNLESS
EVERYBODY WOULD LIKE TO STAY FOR
24 HOURS, YOU KNOW, OR WELL INTO
THE EVENING WE WON'T BE ABLE TO
GET TO ALL OF THE QUESTIONS.
BUT WE ARE CERTAINLY CAPTURING
ALL OF THOSE.
AND SO MAY BE ABLE TO WEAVE THEM
IN.
WE'RE CAPTURING ALL OF THE
WONDERFUL QUESTIONS THAT HAVE
BEEN STIMULATED BY THE WONDERFUL
PRESENTATIONS THAT WE'VE HAD
TODAY.
DID YOU WANT TO COME ON AND
INTRODUCE YOURSELF?
AND LEAD OFF WITH QUESTIONS
PRESSING FROM THE EARLIER
SESSION.
>> THANK YOU, ROBIN AND NANCY.
I DIDN'T SPEAK ENOUGH LAST TIME
SO YOU'RE MAKING ME BE MODERATOR
AGAIN.
YES, SO FIRST OF ALL, YOU WANT
TO THANK EVERYONE FOR A
WONDERFUL PRESENTATION AND
DISCUSSION.
UNFORTUNATELY, DUE TO LACK OF
TIME, WE CAN'T POSSIBLY GET TO
MANY OF THE INTERESTING
QUESTIONS BEING POSED BUT SO
WHAT I'D LIKE TO START OFF THIS
DISCUSSION WITH FOR THE END OF
TODAY'S SESSION, WE HEARD FROM
KASPER AND DAVID ABOUT IMPACTS
OF MATRIX VERSUS MILK MATRIX,
BEFORE THAT STEPHEN TALKED ABOUT
HUMAN MILK, REFERENCE, BUT WE
DID START WITH SESSION 1 WHERE
WE HAD A GROUP OF GREAT
SCIENTISTS TALKING ABOUT THE
DEVELOPMENTAL PHYSIOLOGY OF THE
INFANT THAT WE'RE TRYING TO
FOCUS ON.
I WANT TO GET US BACK TALKING
ABOUT WHAT WE -- WHAT ALL OF US
TALKED ABOUT TODAY, CONTEXT.
SO I WANT TO START BY ASKING
ANYONE WHO WOULD LIKE TO CHIME
IN.
THINKING ABOUT SAFETY
ASSESSMENTS, INTRODUCED
BIOACTIVE MILK CONSTITUENTS,
FUNCTIONALITY MAY BE A
SIGNIFICANT CONSIDERATION, ARE
THERE TOOLS OR FRAMEWORKS THAT
COULD HELP CHARACTERIZE OR
CATEGORIZE POTENTIAL RISKS
ASSOCIATED WITH SPECIFIC KINDS
OF DEVELOPMENTAL PERTURBATIONS
THAT COULD BE IN PLAY, THIS
WOULD INCLUDE CASES WHERE THE
INTENDED USE WITH ANTICIPATED
BENEFIT, WE MEAN, WELL, YOU
KNOW, BENEFITS FOR SOME
INDIVIDUALS DON'T NECESSARILY
MITIGATE RISK FOR OTHERS IN A
POPULATION, AT LEAST IN CONTEXT
OF THE SAFETY, DEALING WITH THE
ENTIRE SET OF SUBPOPULATION WHO
WOULD BE CONSUMING THIS
PARTICULAR INFANT FORMULA.
SO I THOUGHT I WOULD OPEN THE
FLOOR TO ANYONE WHO WANTS TO
MAYBE CHIME IN TO HELP US THINK
ABOUT THIS.
I WOULD APPRECIATE THAT.
SO I'LL STOP AND PLEASE, IF
SOMEBODY WOULD LIKE TO START.
>> I PUT MY VIDEO ON BECAUSE I
WAS FOLLOWING INSTRUCTIONS BUT
SOMEBODY ELSE CAN ANSWER THIS
BETTER THAN I CAN.
>> THAT WILL TEACH YOU.
PLEASE FEEL FREE TO GO AHEAD.
DR. AZAD?
>> I THINK IF THE QUESTION WAS
ABOUT BENEFIT AND
PERSONALIZATION, THE FACT SOME
SUBGROUPS WOULD BENEFIT PERHAPS
FROM CERTAIN ADDITIVES OR
BIOACTIVES, OTHERS WOULDN'T, SO
THE KIND OF BALANCE, DEPENDING
WHO YOU'RE LOOKING AT IS AN
IMPORTANT QUESTION.
WE'VE-LOOKING AT THIS MORE FROM
BASIC UNDERSTANDING OF HUMAN
MILK SIDE, FOR EXAMPLE LOOKING A
GENETIC RISK OR ENVIRONMENTAL
EXPOSURE, SO, FOR EXAMPLE, WE'VE
SHOWN IN OUR COHORT THAT BABIES
WITH FAMILY HISTORY OF GENETIC
PREDISPOSITION, PERHAPS BENEFIT
MORE FROM BREASTFEEDING IN
GENERAL, MAYBE THAT'S CERTAIN
COMPONENTS, WE HAVE NEW DATA
LOOKING AT GENE HMO INTERACTION
SO CERTAINLY HMOs SEEM TO
QUOTE/UNQUOTE BENEFIT CERTAIN
INFANTS MORE THAN OTHERS BASED
ON INFANT'S GENETICS, SO THINK
THERE ARE MANY ELEMENTS THAT
WOULD BE HARD TO DO, HARD TO
ADDRESS IN A CLINICAL TRIAL BUT
I THINK WE NEED TO GO A LITTLE
BIT DOWN THAT ROAD THINKING
ABOUT WHAT DO CERTAIN
POPULATIONS NEED BASED ON THEIR
GENETIC OR ENVIRONMENTAL RISK
FACTORS, IT CAME UP EARLIER
BABIES BORN BY C-SECTION OR
RECEIVING ANTIBIOTICS, SPECIFIC
COMMON SUBGROUPS, EASILY
IDENTIFIABLE, AS OPPOSED TO WE
DON'T KNOW HUMAN GENETICS BUT WE
KNOW WHICH WERE BORN BY
C-SECTION OR GOT ANTIBIOTICS,
PERHAPS NEEDED BY OTHER BABIES
VAGINALLY EXPOSED, FROM A
MICROBIOME PERSPECTIVE.
>> RIGHT.
JUST TO KIND OF COMMENT ON WHAT
YOU JUST SAID, I THINK THAT I
CAN -- AN IDEAL SITUATION, YOU
KNOW, WE COULD POTENTIALLY THINK
ABOUT MAKING FORMULA
PERSONALIZED AND MAYBE IN A FEW
YEARS COULD DO THAT BUT WE DO
ESSENTIALLY HAVE ONE BASIC SET
OF FORMULATIONS THAT'S AVAILABLE
OR THAT'S USUALLY CONSUMED BY
EVERYONE INCLUDING SOME MAY HAVE
PARTICULAR DISPOSITION FOR, YOU
KNOW, PARTICULAR DISEASE OR WHAT
HAVE YOU.
AND I THINK, YOU KNOW, I THINK
THE THING THAT AT LEAST KEEPS ME
UP AT NIGHT IS, YOU KNOW, WHAT
ARE THE -- YOU KNOW, DO WE HAVE
ASSURANCE THAT, YOU KNOW,
INFANTS WHO MAY BE QUOTE/UNQUOTE
NORMAL BUT SAYS SUSCEPTIBLE TO
CERTAIN PERTURBATIONS, ARE THEY
GOING TO BE IMPACTED BY SOME OF
THESE THINGS THAT ARE BEING
ADDED, AND, AGAIN, I THINK THAT
WE AT LEAST CONCEPTUALLY CAN
THINK ABOUT HUMAN MILK, IN A
SENSE THAT IF IT'S IN HUMAN
MILK, COWS MILK, YOU KNOW,
WHAT'S THE PROBLEM?
WE'VE BEEN CONSUMING THIS FOR,
YOU KNOW, HUNDREDS AND HUNDREDS
OF YEARS AND, YOU KNOW, WHAT ARE
WE MAKING A BIG DEAL OUT OF,
SOMETHING LIKE THIS?
AND, AGAIN, MAYBE THERE ARE NO,
YOU KNOW, POTENTIAL RISKS FROM
SOME OF THESE BIOACTIVES, BUT,
YOU KNOW, IF WE ARE THINKING
ABOUT THESE BIOACTIVES, AS
HAVING ASSUMPTIONAL AFFECT,
THAT'S THE SUPPOSITION, A LOT
HAVE SOME PHYSIOLOGIC OR
FUNCTIONAL ROLE, IF THAT'S THE
CASE SHOULD WE NEED TO BE
FOCUSED ON HOW THESE BIOACTIVES
ACTUALLY FUNCTION AND WORK,
CONTEXT OF HUMAN MILK, AND A WAY
TO THINK ABOUT, WELL, WHAT WOULD
HAPPEN IF WE TOOK THIS OUTSIDE
HUMAN MILK, MAKE IT AND PUT IT
IN A FORMULA, AND SO THAT'S
JUST -- DOES ANYONE ELSE HAVE
ANY THOUGHTS, WANT TO CONTRIBUTE
TO SOME OF THESE DISCUSSIONS?
>> I'LL JUST MENTION I THINK
SOMETIMES WE PUT THE CART BEFORE
THE HORSE.
WE STILL DON'T KNOW HOW THIS
VARIATION IN HUMAN MILK
COMPOSITION IMPACTS THE
BREASTFED BABY AND NOW WE'RE
TRYING TO PROJECT TO FORMULA-FED
BABY.
I FEEL LIKE WE NEED TO DO THE
LATTER FIRST, THE FORMER FIRST.
SO I JUST THINK WE'RE NOT THERE
YET.
>> AND ONE SPECIFIC EXAMPLE
WHERE I DON'T REALLY HAVE THE
EXPERTISE MYSELF BUT THAT IS THE
STORY ABOUT 2FL, 2FL NOW BEING
ADDED BUT A NUMBER OF MOTHERS
ARE GENETICALLY, YEAH, NOT ABLE
TO EVEN PRODUCE 2FL.
SO TO ME IT LOOKS LIKE A VERY
ODD HMO TO ADD TO INFANT
FORMULA, I'M NOT AN HMO EXPERT
SO IF SOMEONE ELSE HERE WOULD
LIKE TO COMMENT OR HAS A MORE
DEEPER INSIGHT I WOULD BE VERY
HAPPY TO HEAR.
>> WELL, KASPER, THAT'S WHAT I
WAS ABOUT TO COMMENT, THE
CLASSIC I THINK ABOUT.
YES IT'S FOUND IN HUMAN MILK BUT
ONLY 75% OF MOMS PRODUCE IT,
SHOULD WE GIVE IT TO EVERYONE?
LARS WILL TALK ABOUT IT TOMORROW
SO MAYBE I WON'T SAY MORE.
I HAVE A CLINICAL TRIAL STARTING
WHEN COVID CAN BE OVER IN
ALBERTA, WHEN DONOR MILK, LOOK
AT MATCHING TO SECRETER STATUS,
AND TO SEE IS THAT A BETTER WAY
OF MATCHING AND IT'S INTERESTING
TO TALK TO CLINICIANS IN THE
DESIGN OF THE STUDY, SOME HAVE
GOTTEN THE IMPRESSION 2FL IS
IMPORTANT, THAT'S WHY THEY ARE
ADDING, ALL BABIES SHOULD HAVE
IT, WHY WOULD WE DENY THE BABIES
THIS OLIGOSACCHARIDE?
WE DON'T KNOW YET IF IT'S A GOOD
THING, HARMLESS OR POTENTIALLY A
FACTOR.
>> I HAVE A QUESTION FROM THE
E-MAILERS.
THERE'S A LOT OF THEM.
ONE QUESTION WAS CONSIDERING THE
CHALLENGES OUTLINED WHAT ROLE
DOES PRE-CLINICAL TRIALS HOLD IN
ASSESSING BIOACTIVES, ANYBODY?
>> I WOULD COMMENT ON SOMETHING.
GIVEN HOW DIFFICULT IT IS TO DO
CLINICAL TRIALS,
BIOAVAILABILITY, A GOOD ANIMAL
MODEL MAY EXIST, A NUMBER OF
PENAL -- PEOPLE ON THE CALL,
QUITE USEFUL FROM SAFETY AND
EFFICACY PERSPECTIVE.
I DON'T THINK THAT WE'RE OUTSIDE
OF THE AREA WHICH WE NEED TO DO
PRE-CLINICAL STUDIES, ESPECIALLY
GIVEN THAT THEY HAVE FOCUS ON
THE HUMAN STUDIES, WE CAN'T LOOK
AT EVERYTHING AND EVERYONE.
>> I WOULD AGREE WITH THAT.
THIS IS ONE OF THE ONLY WAYS
WE'RE GOING TO BE ABLE TO LOOK
AT THESE INTERACTIVE AND
SYNERGISTIC EFFECTS IN A
MECHANISTIC WAY.
I THINK THEY ARE CRITICAL.
>> GREAT.
AND SOUNDS LIKE DR. DONOVAN
WOULD LIKE TO JUMP IN.
>> I WILL PRESENT TOMORROW BUT I
AGREE I THINK IT'S A CONTINUUM
AND PARTICULARLY NOW LOOKING AT
ORGAN RATES DERIVED FROM HUMAN
TISSUES, INFANT TISSUES, BUT
GOING TO BE APPROPRIATE
PRE-CLINICAL MODELS ARE REALLY
GOING TO BE NECESSARY AND
INSTRUMENTAL AND SHELLEY
MENTIONED FOR INTERACTIONS AND
MECHANISTIC WORK, SO I THINK
THEY ARE GOING TO CONTINUE TO BE
IMPORTANT.
WE NEED TO BE AWARE OF CAVEATS,
LIMITATION, BUT THEY DO I THINK
ALLOW QUESTIONS THAT WOULD THEN
GO INTO CLINICAL TRIALS.
>> THANKS FOR THAT.
>> I WANTED TO MENTION
ESPECIALLY I THINK THE MODELS
MIGHT BE MORE APPLICABLE,
OBVIOUSLY MOUSE MODELS ARE NOT
RELEVANT TO ANSWER ALL OF THOSE
QUESTIONS.
IMMUNE SYSTEM DEVELOPMENT AND
INTERACTION BETWEEN MATERNAL AND
INFANT IMMUNITY IS QUITE
DIFFERENT ESPECIALLY AS PERTAINS
TO IMMUNOGLOBULIN PASSAGE FROM
THE MOTHER TO INFANT, SO TO
ANSWER THOSE QUESTIONS THAT ARE
IMMEDIATELY RELATED TO
IMMUNOGLOBULIN DEVELOPMENT IN
INFANCY, ANIMAL MODELS,
ESPECIALLY MOUSE MODELS WOULD
NOT NECESSARILY BE APPLICABLE.
IT DEPENDS ON THE QUESTION
YOU'RE TRYING TO ANSWER.
FOR MICE, WELL, FOR HUMANS, FOR
THAT FACT, MOST OF
IMMUNOGLOBULIN G TRANSFER
HAPPENS PLACENTALLY, WHETHER AS
IN MOST MOST TRANSFER HAPPENS
POST-NATALLY IN BREAST MILK, A
FLAVOR OF HOW DRASTICALLY
DIFFERENT IMMUNE SYSTEM
DEVELOPMENT IN EARLY LIFE IS.
ESPECIALLY WHEN IT PERTAINS TO
IMMUNOGLOBULINS.
>> THERE WAS ANOTHER E-MAIL.
ABOUT VEGETARIAN DIETS.
CONSUMER INTEREST AMONG VEGANS,
PLANT-BASED FORMULA, INTERESTED
IN TERMS OF NON-MILK SOURCES OF
INGREDIENTS AND POTENTIAL
EFFECTS GOOD OR CONCERNING IN
THE FIRST SIX MONTHS AND I GUESS
NOT JUST FORMULA BUT ALSO THE
MOM'S INTAKE IF SHE'S
EXCLUSIVELY BREASTFEEDING.
ANY TAKERS?
>> ON THE FORMULA SIDE WE HAVE
TO WORRY ABOUT ESSENTIAL AMINO
ACIDS.
>> UH-HUH.
>> NON-BREAST, IT'S FORTIFIED.
>> THE PRIMARY PROTEIN HAS BEEN
FDA APPROVED OR APPROVED IN MOST
COUNTRIES HAS BEEN SOY.
THERE IS INTEREST IN OTHER
PROTEIN SOURCES FROM DIFFERENT,
ALMONDS AND THAT SORT OF THING.
ANY ATTEMPT TO CHANGE THAT
PARADIGM WOULD REQUIRE ABSOLUTE
COMPLETE FDA EVALUATION
INCLUDING ALL FULL GROWTH
BIOAVAILABILITY BALANCE STUDIES,
WHATEVER, BEFORE WE WANT TO GO
THERE.
PEOPLE LOOKED AT OTHER ANIMAL
SOURCES, MOST NOTABLY GOAT USED
IN EUROPE BUT NOT APPROVED FOR
INFANT USE IN THE UNITED STATES.
I THINK ANYTIME YOU MAKE A MAJOR
CHANGE IN PROTEIN SOURCING
ABSOLUTE COMPLETE EVALUATION OF
ALL ASPECTS OF IT SO I DON'T
THINK THAT WILL HAPPEN SUPER
FAST, ALOE AL -- ALTHOUGH I
DON'T THINK THERE'S A HUGE
NECESSITY THAT CAN'T HAPPEN.
>> I MIGHT JUMP IN AND KIND OF
PULL BACK INTO A MUCH KIND OF
BIGGER PICTURE.
THAT'S ONE ABOUT CONSIDERING THE
SAFETY ASSESSMENT.
HOW DO WE INCORPORATE THIS NEW
INFORMATION THAT'S COMING IN
FROM HUMAN MILK RESEARCH INTO
SAFETY ASSESSMENTS OF
INGREDIENTS THAT TRY TO
REPLICATE THE FUNCTIONALITY OF
SIMILAR COMPONENTS OF HUMAN
MILK?
SO IN OTHER WORDS CAN WE MAKE A
SAFETY CALL WITHOUT
UNDERSTANDING THE FUNCTIONALITY
OF THE CORRESPONDING CONSTITUENT
IN HUMAN MILK?
>> CAN YOU GIVE US AN EXAMPLE?
>> HMM.
EXAMPLES MAYBE K-OTARO OR NANCY?
>> YEAH, I MEAN I CAN'T --
WELL, I CAN'T COME UP WITH A
SPECIFIC WOULDN'T.
FOR OUR GENERAL DISCUSSION, ANY
PROTEIN BASED IMMUNOMODULATORS,
CYTOKINE, THOSE ARE THE TYPE OF
SUBSTANCE WHERE, YOU KNOW, WE
KNOW SOME OF THE FUNCTIONALITIES
BASED ON CONTEXT OUTSIDE OF
INFANT DEVELOPMENT, RIGHT?
WE KNOW A GOOD CHUNK OF WHAT
CYTOKINES DO IN CONTEXT OF
IMMUNE SYSTEM, IN ADULTS OR IN
ANIMALS, BUT WE DON'T REALLY
KNOW WHAT IT'S ACTUALLY DOING IN
THE CONTEXT OF INFANTS.
AND SO THAT WOULD BE A CASE
WHERE WE KNOW ENOUGH ABOUT THE
FUNCTIONALITY OF A PARTICULAR
BIOACTIVE SUBSTANCE, BUT IN A
DIFFERENT CONTEXT.
SO, YOU KNOW, WE CAN MAKE A LOT
OF ASSUMPTIONS, HYPOTHESIS, IN
TERMS OF WHAT IT MIGHT DO, IF IT
IS, SAY, PART OF A HUMAN MILK
CONSTITUENT AND ADDED TO INFANT
FORMULA, A LOT IS SUPPOSITION,
THAT'S WHAT WE'RE THINKING ABOUT
IN TERMS OF GOING FROM
PREGNANCY, ACTIVE BIOACTIVE
SUBSTANCE, PART OF HUMAN MILK,
YOU KNOW, WITHOUT REALLY
UNDERSTANDING WHAT IT'S DOING IN
THE CONTEXT OF HUMAN MILK CAN WE
MAKE ASSUMPTION PUTTING THIS IN
INFANT FORMULA MATRIX IS
EXPECTED TO FUNCTION IN A
SIMILAR WAY.
OR MAY NOT HAVE FUNCTION.
I THINK AL ALL THOSE ARE
IMPORTANT CONSIDERATIONS WHEN
THINKING ABOUT THE RISKS, WHAT
ARE THE RISKS, SO THAT'S KIND OF
I THINK THE POINT OF THAT
QUESTION, I BELIEVE.
I DON'T KNOW IF THAT MAKES
SENSE, SHELLEY.
>> IT DOES, BEING A NUTRITIONIST
THIS IS A HIGHER LEVEL ANSWER,
NOT REAL SPECIFIC.
BUT WE'RE STILL LEARNING WHAT
THE ESSENTIAL NUTRIENTS ARE
DOING.
AND SO I DON'T KNOW AT WHAT
POINT DO WE DECIDE WE KNOW
ENOUGH WHAT SOMETHING IS DOING
TO CALL IT GOOD?
I DON'T KNOW THE ANSWER.
WE'RE STILL LEARNING WHAT
ESSENTIAL NUTRIENTS ARE DOING SO
I DON'T THINK WE SHOULD WAIT,
YOU KNOW, JUST PHILOSOPHICALLY
UNTIL WE UNDERSTAND THE WHOLE
PACKAGE.
YOU NEVER KNOW WHEN YOU'RE
THERE.
>> SURE.
WELL, SHELLEY, LET ME JUMP ON
WHAT YOU JUST MENTIONED AND KIND
OF BRING UP ANOTHER SET OF
DISCUSSION POINTS THAT I HOPE
EVERYONE CAN AT LEAST CHIME IN
ON.
SO, YOU KNOW, FOR MANY OF THE
HUMAN MILK, WHETHER QUANTITATIVE
DATA, WE TYPICALLY WOULD USE,
SAY, A MEAN, STATISTICAL MEAN,
UPPER LIMIT TO USE AS A
REFERENCE VALUE FOR HUMAN MILK,
BUT, YOU KNOW, WE LARGELY IGNORE
LIKE THE LOWEST REPORTED LEVEL.
SO, IS THERE ANY VALUE TO
THINKING, YOU KNOW, SINCE WE
DON'T KNOW INTENDED OR
UNINTENDED EFFECTS OF MANY
CONSTITUENTS, PERHAPS WE SHOULD
USE THE LOWEST REPORTED LEVEL,
AS A TARGET LEVEL TO START OFF
WITH, INSTEAD OF THE MEAN.
YOU KNOW, IF IT'S PROPOSED TO BE
USE FOR INFANT FORMULA.
AND THIS IDEA CONCEPTUALLY,
LOWER LEVELS IN MILK FOR INFANTS
THAT ARE HEALTHY, LOWER LEVELS
IN THEORY SUFFICIENT TO PROVIDE
OPTIMUM INFANT GROWTH AND
DEVELOPMENT.
DO YOU HAVE ANY THOUGHTS?
I DON'T WANT TO SAY CONTRARIAN
VIEW BUT A VIEW THAT'S NOT
ALWAYS DISCUSSED.
WE FIXATE ON THE MEAN AND UPPER
LEVEL AS WELL IT'S GOT TO BE
SAFE AS LONG AS IT'S BELOW THAT.
MAYBE WE SHOULD AT LEAST DISCUSS
POTENTIALLY LOOKING AT LOWEST
VALUES TO GO FORWARD UNTIL WE
KNOW BETTER, OR WE UNDERSTAND
BETTER.
>> IT'S ALMOST LIKE UL APPROACH.
YOU KNOW, WE KNOW THIS LEVEL IS
SAFE.
THAT'S INTERESTING.
THERE'S A POSSIBILITY THOUGH
THAT INFANTS CONSUMING VERY,
VERY LOW -- THE LOWEST LEVELS
MAYBE ARE GENETICALLY DIFFERENT
THAN INFANTS CONSUMING TOP
LEVELS, SOME GENETIC SPECIFICITY
TO MATERNAL/INFANT DYAD.
I WONDER IF THAT WAS DISCUSSED
WHEN A.I.s WERE CONSIDERED AND
INFANT FORMULA REGULATIONS WERE
CONSIDERED.
IF WE KNOW FOR SURE THAT
INFANTS -- ONE OF THE PROBLEMS
HERE HOW DO YOU KNOW THEY ARE
HEALTHY?
I MEAN, JUST BECAUSE THEY ARE
GROWING WELL?
UNLESS WE HAVE SOME SORT OF
BIOMARKER OR BIOINDICATOR, DO WE
KNOW THAT FOR SURE?
DO WE USE A GLOBAL ASSESSMENT OF
HEALTH OR DO WE HAVE A BIOACTIVE
SPECIFIC ASSESSMENT OF HEALTH?
>> I CAN SEE DR. SELA LOOKING TO
JUMP IN.
>> I LOVE HOW SHELLY ASKED THE
HARD QUESTION, WHO IS HEALTHY?
HOW DO WE ASSESS?
I'M NOT A REGULATOR.
IS RISK THE SAME THING AS
SAFETY?
I DON'T PUT C. DIFF IN INFANT
FORMULA, MAKING A JOKE, NO ONE
TAKE THAT SERIOUSLY.
EVERYTHING OF A MINOR RISK IS A
SAFETY CHALLENGE FROM MY HUMAN
NAIVE PERSPECTIVE?
I DON'T KNOW.
AS A REGULATOR YOU WANT ZERO
TOLERANCE FOR RISK.
THERE'S OPPORTUNITY COST.
SOMETHING LIKE WHERE IF -- I'M
MAKING UP ANOTHER EXAMPLE, LET'S
SAY LENTIL PROTEIN WILL ONLY --
OUTCOME 2% LESS IN WEIGHT GAIN
VERSUS BOVINE PROTEIN SOURCE, IS
THAT A RISK?
IT'S NOT A SAFETY ISSUE.
BUT IS IT A RISK TOO?
I DON'T KNOW ENOUGH ABOUT
REGULATORY FRAMEWORKS, WHETHER
OR NOT THESE ARE THINGS THAT GO
INTO POLICY OR NOT.
BUT THESE ARE THINGS I THINK
ABOUT WHEN WE'RE LOOKING TO
INNOVATE IN OUR LABORATORY, AND
MOVING FORWARD WHAT IS IMPORTANT
FOR US TO LOOK AT.
>> LET ME SEE IF I CAN ADDRESS
THE QUESTION.
APRIL, I DON'T KNOW IF YOU'RE
STILL AROUND.
YOU MIGHT BE ABLE TO PARTICIPATE
IN THIS AS WELL.
SO, YES, RISK, THAT'S VERY
SUBJECTIVE FOR SURE.
AND, YOU KNOW, ONE OF THE, YOU
KNOW, CONUNDRUMS WE HAVE IS I
KNOW A LOT OF FOLKS DON'T
UNDERSTAND WHY FDA, WHEN WE HAVE
SAFETY OF FOODS, DON'T DO A
RISK/BENEFIT, RIGHT?
AND PART OF THAT IS BECAUSE FOOD
IS SUPPOSED TO HAVE VERY LITTLE
RISK AS OPPOSED TO A DRUG THAT
MAY HAVE POTENTIAL BENEFICIAL
EFFECT, YOU CAN MITIGATE CERTAIN
RISKS.
IN OTHER WORDS, WE MIGHT BE ABLE
TO SAY, WELL, EVEN IF WE DON'T
UNDERSTAND ALL THE RISKS,
BECAUSE OF THE POTENTIAL
BENEFITS PERHAPS WE CAN IGNORE
THEM.
IN TERMS OF FOOD SAFETY THAT IS
SOMETHING WE DON'T DO.
IN OTHER WORDS, IT'S SUPPOSED TO
BE SAFE.
PERIOD.
INDICATOR IN THE PRE-SESSION, WE
HAVE A STANDARD DEFINITION OF
WHAT SAFETY IS IN TERMS OF
REGULATION, THAT'S REASONABLE
CERTAINTY OF NO HARM.
NO HARM COULD MEAN A LOT OF
THINGS.
SOME MAY FOCUS ON A PARTICULAR
ADVERSE EFFECTS THAT MAYBE
OTHERS DON'T, MAY NOT FOCUS ON
BUT I THINK THE KEY THING HERE
WITH RESPECT TO CONVERSATION
WE'RE HAVING, WE'RE TALKING
ABOUT INFANTS PARTICULARLY
VULNERABLE.
THAT COULD HAVE THE RISK -- RISK
COULD HAVE LONG-TERM SUBTLE
IMPACT THAT COULD BE DEFINED AS
ADVERSE EFFECT.
AND WHEN WE ARE DEALING WITH,
LET'S SAY, ADULT POPULATION WE
MAY NOT BE AS CONCERNED ABOUT
SOME POTENTIAL RISK BUT NOW
WE'RE TALKING ABOUT INFANTS,
VERY EARLY, AND THAT'S WHY THE
SESSION 1 WAS INFORMATIVE TO
KIND OF GET A BASELINE IN TERMS
OF WHAT WE'RE TALKING ABOUT.
AGAIN, THAT IS A STRUGGLE.
ARE WE -- YOU KNOW, THINKING
ABOUT RISK CORRECTLY?
THAT REALLY, YOU KNOW, THAT
REALLY IMPACTS THE REST OF AN
INFANT'S LIFE.
SO, AGAIN, THIS IS WHY WE'RE
HAVING -- WE'RE GLAD TO HAVE
THIS WORKSHOP, THESE ARE
CONVERSATIONS AND DISCUSSIONS
THAT WOULD BE HELPFUL FOR US.
>> GREAT.
THANKS SO MUCH, KOTARO.
WHY DON'T WE, NANCY, I DON'T
KNOW IF ANOTHER QUESTION HAS
POPPED UP.
WE HAD EARLIER QUESTIONS.
>> THIS IS JOE.
A REAL QUICK COMMENT ON SOME
THINGS WE'VE BEEN TALKING ABOUT
HERE.
I'M THINKING THAT WE MAY BE
CHERRY PICKING THE COMPONENTS OF
HUMAN MILK THAT WE THINK ARE
GOOD FOR THE BABIES, OKAY?
FOR EXAMPLE, BIFIDOBACTERIA,
LACTOBACILLUS, HUMAN MILK
OLIGOSACCHARIDES.
IF YOU LOOK AT THE COMPOSITION,
FOR EXAMPLE MICROBES, YOU SEE
CLOSTRIDIUM, E. COLI, AND
PERHAPS SOMEBODY WHO IS MORE ON
THE IMMUNOLOGIC SIDE COULD REPLY
TO THAT FROM THE STANDPOINT THAT
IF WE LEAVE THOSE THINGS OUT, IF
WE'RE NOT THINKING ABOUT THEM,
COULD WE BE CAUSING AN IMBALANCE
IN THE IMMUNE SYSTEM AT A LATER
POINT IN TIME?
SO IT'S BEEN FOUND TICKLING
TOLL-LIKE RECEPTORS IS SOMETHING
VERY IMPORTANT AND SOME TOLL
LIKE RECEPTOR AGONISTS MAY
ACTUALLY BE HELPFUL.
SO IS THIS SOMETHING THAT WE
SHOULD BE THINKING ABOUT?
>> YEAH, BEFORE WE GO TO NANCY,
PLEASE GO AHEAD, KIRSI.
>> I WOULD HAVE TO THINK A
LITTLE BIT ABOUT THE TLP
EXAMPLE.
SINCE I SEE A QUESTION THAT SORT
OF RELATES TO THIS IN THE CHAT,
FROM THE E-MAILS, WHICH IS
ASKING SOMETHING THAT RELATES TO
THIS, I'LL REPEAT IT SO IT HAD
TO DO WITH ASKING MY OPINION ON
SUPPLEMENTATION OF PROTEIN
ANTIGENS TO INFANT FORMULA
VERSUS SUPPLEMENTATION OF
IgAs, SPECIFIC TO KNOWN
ALLERGENS.
WHY I'M THINKING, IT ACTUALLY
RELATES TO THE COMMENT, A
PERFECT EXAMPLE HERE.
BREAST MILK HAS IgA SPECIFIC
TO FOOD ANTIGENS.
WE KNOW THAT.
ALL MOMS HAVE IgA TO LET'S SAY
BOVINE PROTEINS.
50% OF MOTHERS ALSO HAVE
MEASURABLE LEVELS OF BOVINE
PROTEINS IN THEIR MILK, IN THEIR
BREAST MILK.
IN OTHER WORDS, THE WAY INFANT
IS LIKELY SEEING THIS FOREIGN
PROTEIN AS AN EXAMPLE IS, BETA
LACTOGLOBULIN, INTRODUCED WITH A
SPECIFIC ANTIBODY, OKAY?
IN OTHER WORDS, IF YOU INTRODUCE
ONE OF THESE PROTEINS IN THIS
EQUATION TO FORMULA, BUT NOT THE
OTHER, I'M NOT SURE WHAT THE
CONSEQUENCES WOULD BE.
MAYBE THERE WOULD NOT BE
SIGNIFICANT CONSEQUENCES BUT
THIS IS WORTH THINKING ABOUT IT,
IN FACT.
AND ACTUALLY TO ANSWER THE
QUESTION THEN THAT I THINK WAS
MEANT TO QUESTION IS, YOU KNOW,
WHAT'S THE DIFFERENCE?
WELL, ADDING PROTEIN ANTIGENS,
AGAIN, AS AN EXAMPLE, INTO
INFANT FORMULA, WOULD INTRODUCE
THIS PROTEIN ACTIVELY TO THE
INFANT IMMUNE SYSTEM, HOPE, I
BELIEVE, WOULD BE TO TOLERIZE
IMMUNE SYSTEM AGAINST THIS
PEANUT PROTEIN WHICH COULD NOT
HAPPEN AND WORD IS STILL OUT
THERE WHETHER THAT HAPPENS OR
NOT.
ESPECIALLY CONSIDERING TO PEANUT
PROTEIN LEVELS ARE VERY SMALL.
SO IT'S AN ACTIVE FORM OF
TOLERANCE DEVELOPMENT, IT WOULD
HOPE TO INDUCE.
NOW, ON THE FLIP SIDE YOU COULD
SENSITIZE AN INFANT, THAT ROUTE
AS WELL.
IN CERTAIN SITUATIONS THAT WOULD
BE THE WORRY.
AT THE SAME TIME INTRODUCING
IgA SPECIFIC TO PEANUT IN
FORMULA, FOR EXAMPLE, MIGHT HAVE
MULTIPLE DIFFERENT MECHANISMS.
FIRST OF ALL, SOME OF OUR WORK
HAS SHOWN THAT SPECIFIC IgA TO
FOODS, FOR EXAMPLE, CAN AT LEAST
IN CULTURE MODELS PREVENT
EXCESSIVE UPTAKE OF THE SPECIFIC
ANTIGEN TO THE EPITHELIAL CELLS,
CAN KIND OF PREVENT EXCESSIVE
UPTAKE OF PROTEINS IN THE SORT
OF VULNERABLE PERIOD IN EARLY
INFANCY.
AT THE SAME TIME WE KNOW THAT
SPECIFIC IgAs IN BREAST MILK
CAN PLAY A BIG ROLE IN THE
HOMEOSTASIS OF DIFFERENT
BACTERIA, FOR EXAMPLE, AND CAN
REALLY ENFORCE BARRIER FUNCTION
OF THE GUT.
AND THIRDLY THERE IS SOME DATA
SUGGESTING THAT IgA IN COMPLEX
WITH SPECIFIC ANTIGENS COULD
ACTUALLY POTENTIALLY BE UPTAKEN
INTO THE IMMUNOCOMPARTMENT IN
ORDER TO POTENTIALLY EDUCATE THE
IMMUNE SYSTEM ABOUT THIS
ANTIGEN.
SO THIS IS JUST AN EXAMPLE OF
DIFFERENT MECHANISMS THAT THESE
FACTORS IN BREAST MILK HAVE AND
THERE'S INTERACTION BETWEEN THEM
AS WELL.
>> GO AHEAD, DAVID.
>> THANK YOU.
I WANT TO QUICKLY RESPOND TO
WHAT JOE POSITED EARLY ABOUT
CHERRY PICKING AND LABELING
THINGS, I'LL EXTEND, GOOD VERSUS
BAD.
WE CAN SEE AS PEOPLE MAKE FOOD
CHOICES CONSTANTLY EVALUATING
ENVIRONMENT, LABELING FOODS GOOD
VERSUS BAD, IT'S EXHAUSTING WHEN
YOU START THINKING HOW WE
INTERACT WITH FOODS, LED TO
ANXIETY AND CONSTERNATION WITHIN
OUR SPECIES ACTUALLY.
WE'RE CONSTANTLY EVALUATING
THAT.
WE'RE EVALUATING OUR ENVIRONMENT
AND SCIENTISTS LOOKING AT
MICROBIOME, LOOKING AT BUGS,
THAT'S A GOOD BUG, A BAD BUG,
THROWING DOWN THE SMALL PICTURE,
NOT LOOKING AT BALANCE TO THE
COMMUNITY, NOT LOOKING AT
PHENOTYPE, HOST GENETICS, ALL
THE STUFF, RIGHT?
ALL THE BIG PICTURE STUFF AS
WELL.
WE HAVE A JOB TO DO.
REGULATORS AND PARTITIONERS THAT
WE NEED TO DO THINGS THAT KEEP
OUR SOCIETY RUNNING, IN A WAY SO
THERE'S A CREATIVE TENSION
BETWEEN THAT.
I CAN SAY PHILOSOPHICALLY
THERE'S NO SUCH THING AS GOOD
VERSUS BAD BUGS BUT DO
SOMETHING IN CLINIC AND BROADER
SOCIETAL CONTEXT BUT WHAT JOE
WAS PUTTING FORTH THAT'S
IMPORTANT THAT WE ONLY HAVE
ACCESS TO A VERY SMALL WINDOW
INTO THINGS, FOR US TO BE HUMBLE
AND NOT SAY THAT THAT IS A BAD
BUG, THAT OUTCOME IS BAD, IT
GOES BACK TO WHAT YOU SAY THE,
KOTARA, ABOUT HARM.
YOU SAID RIGHT AWAY IT'S
SUBJECTIVE, BUT THERE IS GOING
TO BE A BUG IN YOUR GUT THAT'S
GOING TO BE HARMFUL IN ONE
PERSON OF CONTEXT, IS THAT
HARMFUL -- IS THAT ZERO
TOLERANCE FOR THAT?
I DON'T HAVE AN ANSWER.
THAT'S WHY MY HAT'S OFF TO
REGULATORS, THANK YOU FOR YOUR
WORK, BUT LOOKING AT THE
MICROBIOME, WE NEED TO STEP BACK
AND STEP AWAY FROM THOSE WHO
HAVE THE ABILITY TO DO SO, MAYBE
ENVIRONMENTAL SCIENTISTS, THAT'S
BEEN HELPFUL, MY PERSPECTIVE.
>> NANCY?
SO, SOMEBODY ELSE?
I KNOW NANCY WAS GOING TO CHIME
IN OR MOVE, IS THAT OKAY?
>> SOMEBODY ELSE WANTS TO
ADDRESS THAT, GO RIGHT AHEAD.
I HAVE ANOTHER QUESTION.
>> NANCY, JUST BEFORE YOU GO TO
THE NEXT QUESTION I WANT TO JUST
TOUCH ON WHAT DAVID JUST SAID,
WHICH IS YOU'RE RIGHT, THERE'S
NO CONCEPT WE CAN HANG A HAT ON
IN TERMS OF ABSOLUTE NO-RISK
BASIS, THAT'S WHY OUR DEFINITION
OF WHAT SAFETY IS, WHICH IS
REASONABLE CERTAINTY OF NO HARM,
IS SO IMPORTANT, THAT WORD
"REASONABLE."
EVEN THOUGH WE CAN HAVE
DISCUSSIONS ABOUT WHAT WE CAN
INTERPRET, WHAT REASONABLE IS,
BUT I THINK IT IS A FAIRLY HIGH
STANDARD.
BUT, AGAIN, THE REASONABLE
QUALIFIER IS AN IMPORTANT ONE,
WE CAN BE 100% CERTAIN THERE'S
NO RISK, THAT'S A GOOD POINT.
SORRY, NANCY.
>> NO PROBLEM.
THIS IS FOR THE SESSION 1
PEOPLE.
WE ONLY COVERED A FEW BIOLOGIC
SYSTEMS THAT ARE LIKELY TO BE
IMPACTED BY NUTRITION AND
BIOACTIVES, I THINK WE ONLY
COVERED FOUR.
ARE THERE OTHER AREAS OF NORMAL
DEVELOPMENT THAT FUTURE RESEARCH
SHOULD CONSIDER TO DETERMINE IF
THERE'S AN IMPACT OF THE
BIOACTIVES?
I DON'T KNOW IF MANDY WANTS TO
TAKE THAT OR SOMEBODY ELSE.
WE COVERED G.I., MICROBIOME,
IMMUNE AND NEUROLOGIC.
>> SO ONE WE DIDN'T TALK ABOUT
THAT I THINK IS IMPORTANT IS
METABOLIC.
CARDIOMETABOLIC.
DATA BREASTFEEDING AS IMPACT ON
BLOOD PRESSURE LATER ON IN
CHILDHOOD, FOR EXAMPLE.
AND ALSO APPETITE REGULATION, SO
THEREFORE WEIGHT GAIN, THESE ARE
IMPORTANT THINGS TO BE THINKING
ABOUT.
THEY RELATE TO NOT ONLY THE
COMPONENT OF THE MILK BUT METHOD
OF FEEDING.
THERE'S INTERESTING WORK AROUND
BOTTLE FEEDING, WHETHER HUMAN OR
FORMULA OR DONOR MILK,
DIFFERENCES IN THE ACTIVITY OF
FEEDING, BOTH INTAKE OF INFANT
AND ALSO INTERACTION WITH THE
MOTHER, THE CAREGIVER.
THOSE WE NEED TO BE MINDFUL OF.
COMPOSITION FRONT RELATABLE TO
FORMULA, APPETITE REGULATING
HORMONE, LEPTIN, INSULIN, HOW
THOSE MIGHT AFFECT APPETITE
REGULATION.
>> THIS IS SHARON.
I WOULD ADD DATA EMERGING FROM
GERM-FREE ANIMALS, UNDERSTANDING
INTERACTIONS, AND THE FOUR
SYSTEMS YOU MENTIONED, I HAVE IN
MY TALK, THEY ARE ALL
INTERRELATED.
THE MICROBIOME AFFECTS THE GUT,
THE IMMUNE SYSTEM AFFECTS THE
BRAIN.
RATHER THAN GETTING AWAY FROM
CONCEPT OF ONE BIOACTIVE WE ALSO
NEED TO CONSIDER IT'S GOING INTO
A COMPLEX SYSTEM.
SO WE'VE BEEN TALKING ABOUT
SYSTEMS BIOLOGIES WITHIN SYSTEMS
BIOLOGIES, AND AGAIN I THINK
THIS IS WHERE PRE-CLINICAL
ANIMAL MODELS CAN HELP BECAUSE,
YOU KNOW, ALSO I WOULD LIKE TO
SEE STUDIES THAT WE DON'T JUST
GO IN, EAT A BIOACTIVE AND LOOK
AT IMMUNE FUNCTION.
YOU GO AND LOOK AT IMMUNE
FUNCTION, GI DEVELOPMENT,
MICROBIOME, COGNITIVE AS MUCH AS
YOU CAN BECAUSE I TOTALLY AGREE,
AND THEN MEGAN BROUGHT IN
METABOLIC, ALL INTERRELATED,
ALSO THE CONCEPT MANDY
MENTIONED, CRITICAL WINDOWS,
DISASSOCIATION WITH HMOs,
MICROBIOME.
DIFFERENT HMOs ASSOCIATED WITH
DIFFERENT COGNITIVE OUTCOMES,
DIFFERENT TIME POINTS, IS THAT
BECAUSE THAT'S THE CRITICAL
WINDOW, IS IT BECAUSE THAT'S
WHEN IT'S BEING MEASURED?
YOU KNOW, I THINK IT'S REALLY
THE FACT THAT IT'S SO DAUNTING
THINKING ABOUT THE TYPE OF
EVIDENCE THAT WE, IN MY OPINION,
WE NEED TO BE PUSHING THE BALL
AROUND THE FIELD BECAUSE
THINKING ABOUT DATA SCIENCE I
FEEL LIKE APPROACHING THIS, THE
OLD WAY WE APPROACH NUTRITION,
VERY REDUCTIONIST, ONE NUTRIENT
AT A TIME, WHEREAS THINK ABOUT
DIETARY GUIDELINES, RESPOND TO
DIETARY PATTERNS, HOLISTIC
VIEWS.
TO ME HUMAN MILK AND INFANT
FORMULA ARE SYSTEMS.
WE KNOW SYSTEMS ARE DIFFERENT
BUT I THINK AS MUCH AS POSSIBLE
WE NEED TO START APPLYING THE
SYSTEMS' THINKING TO THIS, AND
KASPER'S TALK ABOUT HEATING
PROTEINS, THEY START TO COME
TOGETHER, SO I HOPE WE CAN GET
ONE FROM ONE BIOACTIVE, ONE
OUTCOME, MORE TO HOLISTIC VIEWS.
>> TO ADD TO THAT WE TALK ABOUT
ORGAN SYSTEM SPECIFIC OUTBUT
THERE ARE HOLISTIC OUTCOMES THAT
ARE NOT SPECIFIC TO ANY ONE
PATHWAY OR BIOLOGICAL IMPACT,
BUT CAN GIVE SUMMARY MEASURE OF
THE IMPACT ON OVERALL HEALTH, SO
QUALITY OF LIFE, SORT OF THE
CONSTRUCTS OF POSITIVE HEALTH,
SUMMATIVE MEASURES COULD BE
INCORPORATED, IN COMBINATION
WITH OTHER ORGAN-SPECIFIC
OUTCOME MEASURES.
>> ANY OTHER COMMENTS OR
THOUGHTS ON THIS THREAD?
THERE WAS ANOTHER QUESTION THAT
HAD COME IN EARLIER VIA E-MAIL.
IN TERMS OF ADDING MICROBES TO
FORMAL, THAT BEING PARTICULARLY
CHALLENGING, READY-TO-FEED
FORMULAS ARE STERILIZED IF
MICROBES ADDED, REFRIGERATION,
ADDING HUGE COST AND
DISTRIBUTION, STORAGE, FOR
INSTANCE WHEN ADDING TO POWDER,
FOR HOW LONG ARE MICROBES
VIABLE, IS VIABILITY AFFECTED BY
STORAGE?
EITHER IN STORE OR AT HOME.
>> YES, VIABILITY IS AFFECTED BY
STORAGE.
THERE IS A CURRENT PERSPECTIVE
THAT WE HAVE TO BE AWARE IN THE
MOMENT WHAT IS THE TECHNOLOGICAL
LIMITATIONS AND VERY IMPORTANT
ECONOMIC LIMITATIONS WHAT WE'RE
ABLE TO ACCOMPLISH ON A WIDE
SCALE.
PRECISION NUTRITION HAS TO BE
ECONOMICALLY VIABLE TO
DISSEMINATE DOMESTICALLY AND
GLOBALLY.
YES, THOSE ARE LIMITATIONS THAT
POTENTIALLY COULD BE SOLVED.
THAT'S WHY WE ASKED THE
QUESTIONS, COULD WE SOLVE THOSE
AND DO WE WANT TO?
IS THIS SOMETHING WE'RE
INTERESTED IN DOING?
THESE ARE ALL GOOD QUESTIONS
THAT WERE RAISED BY THE
INDIVIDUAL.
>> WE'LL GIVE DAVID A CHANCE.
GO AHEAD.
>> THERE WAS A QUESTION ABOUT
THE ENCAPSULATION OF PROBIOTICS
IN INFANT FORMULA, THEY WANTED
DETAILS ON STUDIES AND PRIMARILY
PROCESSING AND STORAGE AND
WHETHER YOU NEED MORE WORK ON
THE CLINICAL SIDE.
DID YOU UNDERSTAND?
>> I DID, YES.
I AGREE WITH THOSE COMMENTS THAT
PRIMARILY THE WORK HAS BEEN DONE
MORE ON THE FOOD ASPECT,
DEVELOPMENT OF PRODUCT ITSELF,
AND METRICS ONE DOES WITHOUT THE
HOST.
SO TRADITIONALLY THIS IS THE WAY
IT WAS EXPLAINED TO ME, FOOD
SCIENCE WAS DOING EVERYTHING
BEFORE IT HITS THE INDIVIDUAL'S
LIPS AND NUTRITION IS OUTWARDS,
I LOOK AT A CONTINUUM WHICH
DOESN'T MEAN I'M MORE
ENLIGHTENED, JUST THE WAY I COME
TO TAKE A LOOK.
I DO AGREE THERE NEEDS TO BE
MORE WORK ON CLINICAL OUTCOMES,
WHY WE DO THIS, IS THIS
IMPORTANT OR SOMETHING WE'RE
JUST DOING BECAUSE WE CAN DO IT
TOO.
THERE HAS TO BE MORE WORK IN
TERMS OF OUTCOMES, SOMETHING
WE'RE ABLE TO MEASURE BECAUSE
WE'RE ABLE TO MEASURE IT EASILY.
THOSE ARE QUESTIONS THAT WE
ALWAYS ASK SCIENTISTS,
CONSTANTLY ASK ALMOST EVERY
SINGLE DAY.
>> THANK YOU.
>> I WANT TO BE SURE TO GIVE
FOLKS TIME.
SOME OF THESE QUESTIONS TAKE A
LITTLE TIME TO PERCOLATE AS
WELL.
THERE WAS ANOTHER QUESTION ALSO,
IS THERE A WAY TO SORT OR
CATEGORIZE BIOACTIVE MILK
CONSTITUENTS INTO CLASSES IN
ORDER TO IDENTIFY THOSE FOR
WHICH WE HAVE MORE OR LESS
CONFIDENCE, WE DON'T NEED
INFORMATION ABOUT FUNCTIONALITY
IN THE INFANT G.I. SYSTEM.
CLASSIFICATION, CATEGORIZE,
CONSTITUENTS.
>> MEANING WE ALREADY CLASSIFY
THEM BUT I'LL GET BACK TO WHAT'S
BEEN SAID.
I THINK WE NEED TO STOP DOING
THAT, UNLESS THE QUESTION HAS
MORE TO DO WITH ARE THERE
CERTAIN BIOACTIVES THAT WE
ALREADY UNDERSTAND, SO WELL,
THAT, I DON'T KNOW, MAYBE
FURTHER ALONG IN SCIENCE.
I THINK WE NEED TO GET AWAY FROM
THIS.
I SHOWED YOU THE VENN DIAGRAM,
THESE COMPONENTS ARE LIKELY
DOING MULTIPLE THINGS.
AGAIN, I SEE A NOTE FROM ASHLEY.
YES, THAT WAS THE INTENTION.
MAYBE-- I DON'T KNOW, DO WE EVER
KNOW EVERYTHING WE NEED TO KNOW
ABOUT SOMETHING?
AGAIN, WE'VE TALKED ABOUT THIS
BEFORE, AT WHAT POINT DO YOU
KNOW ENOUGH TO CONSIDER?
THAT'S I'M SURE DEPENDENT ON THE
COMPONENT.
>> WE'RE PRETTY GOOD AT WATER.
>> I FEEL LIKE THE HASHTAG #FOR
TODAY, THAT'S A MILLION DOLLAR
QUESTION.
>> THAT'S A GOOD QUESTION!
>> DAVID, GO AHEAD.
YOU MAY BE ON MUTE.
I'M NOT HEARING YOU.
I'M NOT HEARING YOUR SOUND.
I'M SORRY, WE'RE NOT HEARING
YOU.
I DON'T KNOW IF THERE'S
SOMETHING THAT OUR TECH FOLKS
CAN HELP WITH, WITH THAT.
NO.
PERHAPS IF YOU WOULD LIKE, YOU
COULD TYPE YOUR COMMENT INTO THE
CHAT AND WE COULD READ IT OUT IF
THAT WOULD BE HELPFUL.
SHELLEY, WHILE YOU WERE TALKING
BEFORE, THERE HAD BEEN A
QUESTION EARLIER ABOUT THE
VARIATION IN PROTEIN OVER THE
COURSE OF THE DAY THAT YOU HAD
MENTIONED IN YOUR TALK EARLIER.
OVER THE COURSE OF THE DAY WHAT
DOES THAT MEAN FOR INFANT
FORMULA DEVELOPMENT?
DO WE NEED THAT VARIATION IN
INFAN FORMULA PRODUCTS,
RELEVANT, FEASIBLE, UNSAFE TO
HAVE STANDARD PROTEIN
CONCENTRATIONS?
>> THAT QUESTION HAS BEEN ASKED
ABOUT MILK FAT FOR YEARS AND WE
DON'T HAVE THE ANSWER.
STUDIES HAVEN'T BEEN DONE, AS
FAR AS I KNOW.
I MEAN, MAYBE THEY HAVE BEEN AND
I HAVEN'T SEEN THEM, BUT ARE
THERE, YOU KNOW, ARE THERE
MEASURABLE DIFFERENCES IN
INFANTS WHO ARE FED LOW TO HIGH
FAT MITTING -- MILK OVER A FEED
OR DAY?
I DON'T KNOW THAT THESE STUDIES
HAVE BEEN DONE.
UNTIL WE FIND OUT WHICH
BIOACTIVE PROTEINS ARE GOING UP,
IS IT ALL, IS IT SOME, WE WON'T
BE ABLE TO ANSWER THAT.
HASHTAG #GOODQUESTION.
>> THERE IS SOME DATA, HIGH MILK
MOTHERS, PRODUCERS AND BABIES,
DIFFERENCES IN GROWTH, THERE'S
ALSO SOME DATA IN PREMATURE
INFANTS SUGGESTING HIGH MILK
SUPPORTS BETTER GROWTH.
THERE ARE A LITTLE BIT OF DATA
ON THAT TOPIC BUT NOT
NECESSARILY TO WHAT YOU'RE
GETTING AT.
GOOD DATA SUGGESTS HIGHER FAT
MILK ASSOCIATED WITH HIGHER
GROWTH MILL, FOR 20 YEARS,
FULL-TERM INFANTS A LITTLE
DIFFERENT.
>> AMONGST WOMEN THIS IS A HUGE
DEAL.
DO YOU GOOGLE THIS, YOU GET A
MILLION HITS, ALL MOMS NOW ARE
ALL SCARED, THEY NEED TO MAKE
SURE THEY ARE GETTING ENOUGH
HIGH MILK, THERE'S WAYS TO DO
THAT, YOU KNOW, WE GOT TO BE
CAREFUL ABOUT THAT.
BREASTFED BABIES TEND TO GROW
WELL REGARDLESS OF HOW THEY ARE
FED AND WHETHER THEY ARE FED
FREQUENTLY.
THE DIFFERENCE IN MILK FAT HAS
MORE TO DO WITH HOW OFTEN BABIES
ARE FED AND HOW FULL THE BREAST
IS, IT HAS LESS TO DO WITH JUST
THIS HIGH MILK KIND OF ISSUE.
>> IT GETS TO THE FORMULA ISSUE
OF GROWTH RATES, WHAT IS THE
GROWTH RATE WE'RE SEEKING IN FDA
GROWTH STUDIES BECAUSE THERE'S A
HUGE NATURAL VARIABILITY, DOES
2-GRAM PER DAY MAKE DIFFERENCE,
SOME BREASTFED BABIES GROW
REALLY RAPIDLY INITIALLY AND
SLOW DOWN, VERY DIFFERENT
PATTERNS.
EVEN THE STANDARD OF GROWTH
NEEDS CAREFUL THOUGHT.
>> CAN I JUMP IN AGAIN?
>> YES.
>> WE CAN HEAR YOU.
>> WONDERFUL.
>> TERRIFIC.
>> I WAS GOING TO SAY SOME OF
THE THINGS THAT HAVE COME UP FOR
ME, PARTICULARLY AFTER KASPER'S
TALK, THERE'S A LOT OF DIFFERENT
HEAT TREATMENTS APPLIED TO
FORMULA MILK PROTEINS, AND THAT
THOSE HAVE ARRAY OF EFFECTS ON
AGGREGATION, STRUCTURE,
GLYCATION.
WE'RE NOT CURRENTLY REGULATING
IN TERMS OF WHICH OF THOSE
PROCESSES ARE ALLOWED FOR
FORMULAS.
AND SO THAT'S KIND OF SETTING
SOME HISTORICAL PRECEDENT.
AND I THINK, YOU KNOW, WE
TALK -- WE CAN TALK ABOUT
POTENTIAL STUDIES THAT MIGHT
NEED TO BE DONE UNTIL THE COWS
COME HOME, SO MANY AVENUES TO
THINK ABOUT, BUT, YOU KNOW, HOW
DO WE BALANCE THAT WITH THE NEED
FOR INNOVATION IN THE INDUSTRY?
AND HOW DO WE AVOID
DISCOURAGING, YOU KNOW, ALL THE
POTENTIAL COMPANIES THAT WANT TO
INNOVATE IN THE SPACE, WANT TO
DEVELOP PRODUCTS?
HOW DO WE BALANCE SORT OF THE
POTENTIAL EFFECTS OF THOSE, YOU
KNOW, SPECIFIC PROTEINS OR
COMPONENTS THAT THEY MIGHT WANT
TO ADD COMPARED WITH THE
VARIABILITY THAT MIGHT ALREADY
EXIST IN THE SYSTEM, YOU KNOW,
THINKING ABOUT HOW DIFFERENT
PROTEINS OR DIFFERENT COMPONENTS
ARE ADDED.
IF WE OVERREGULATE THEN MIGHT
THAT LIMIT POTENTIAL FOR
INNOVATION BUT ALSO FOR US TO BE
ABLE TO SEE THE EFFECTS OF SAID
INNOVATION?
SO TO -- IF THERE IS A COMPANY
THAT ADDS SOME COMPONENT TO
FORMULA THEN WE CAN START
COMPLETING STUDIES THAT COMPARE
THE FORMULA WITH AND WITHOUT
SAID COMPONENT.
AND SO IT COULD ALLOW US TO
PROCEED FASTER IN TERMS OF
DISCOVERY.
THAT'S SOMETHING TO CONSIDER
FROM MY PERSPECTIVE, YEAH.
>> I'M HAPPY TO ADD TO WHAT
DAVID WAS JUST SAYING BECAUSE I
THINK IT'S AN INTERESTING
PERSPECTIVE.
I WAS STILL A BIT THINKING ABOUT
KOTARO'S COMMENT MAYBE WE SHOULD
CHOOSE LOWEST LEVEL WE FIND IN
BREAST MILK BECAUSE THAT'S
PROBABLY SAFE, BUT HOW DO WE
KNOW EACH BABY AND EACH MOTHER
ARE PERFECTLY MATCHED?
AND IS THE INFANT NOT JUST ABLE
TO DEAL WITH MILK WITH A
VARIABLE COMPOSITION SO DO WE
HAVE TO WORRY OR A SLIGHTLY
HIGHER OR LOWER LEVEL COMPONENT
JUST HOW NATURE WORKS AND WHAT
AN INFANT WOULD BE ABLE TO DEAL
WITH WHEN IT'S BEING CONSUMED.
>> THIS IS JOE.
THIS IS GETTING BACK TO THE
QUESTION ABOUT THE COMPANY JUST
ADDING MATERIAL TO THEIR
FORMULAS.
SO HISTORICALLY, THERE HAVE BEEN
SOME EXAMPLES OF THAT.
ONE EXAMPLE IS ADDING
NUCLEOTIDES, ANOTHER EXAMPLE IS
GOS-FOS STORY, WHICH THERE ARE
SEVERAL COMPANIES WHO HAVE ADDED
THOSE, WITHOUT REALLY GOOD DATA
THAT THEY HELP.
AND SHOULD THERE BE SOME KIND OF
A CUTOFF IN TERMS OF ADDING
THINGS BECAUSE THEY SEEM TO MAKE
SENSE, AND I THINK THAT'S THE
QUESTION THEY WERE GETTING AT.
AND I HAVE SOME CONCERN ABOUT
THE COMPANIES JUST ADDING
SOMETHING WITHOUT HAVING
EVIDENCE THAT IT ACTUALLY HAS
SOME FORM OF EFFICACY.
>> WELL, I WAS GOING TO SAY SO
LIKE, YES, I AGREE WITH YOU THAT
WE NEED TO -- IF WE'RE GOING TO
ADD SOMETHING TO A FORMULA WE
NEED TO ESTABLISH IT HAS SOME
POTENTIAL FOR BENEFIT.
BUT MANY NOT HAVE A REQUIREMENT
THAT, YOU KNOW, YOU HAVE TO DO
EVERY POSSIBLE STUDY TO EVALUATE
POTENTIAL BENEFIT.
WE CAN THINK ABOUT LONGER TERM
STUDIES LIKE THOSE THAT MIGHT
TAKE AN ENTIRE LIFETIME TO
EVALUATE THE OVERALL EFFECTS OF
CHANGE, RIGHT?
HOW DO WE -- WE HAVE TO THINK
ABOUT HOW A BAR WOULD BE SET.
>> I THINK ONE OF THE CONCERNS
IS THAT A COMPANY CAN JUST PUT
SOMETHING INTO A FORMULA THAT
SEEMS TO MAKE SENSE.
SO, FOR EXAMPLE, NUCLEOTIDE
STORY OR GOS-FOS STORY, SO YOU
MAY NOT SHOW EFFICACY BUT
CERTAINLY THE COMPANIES WILL END
UP MARKETING THIS AND SAY THAT
WE HAVE PUT THIS IN OUR FORMULA
AND WE ARE ONLY ONES WHO HAVE
THIS IN OUR FORMULA.
WITHOUT SHOWING ANY EVIDENCE OF
BENEFIT.
AND I'VE SEEN THIS IN HISTORY,
LAST 30+ YEARS.
AND IT'S BOTHERSOME.
>> YEAH, I AGREE BUT FROM
ANOTHER PERSPECTIVE, YOU KNOW, I
WAS THINKING, YOU KNOW, ONE
THING IS, OH, IT SHOULD BE
SOMETHING THAT ALREADY EXISTS IN
HUMAN MILK AND THAT WE'RE, YOU
KNOW, RECREATING HUMAN MILK BUT
IF THERE'S SOME COMPONENT THAT
MIGHT HAVE SIMILAR EFFECTS TO
THE COMPONENTS IN HUMAN MILK,
PERHAPS THEY WOULD BE GOOD
SUBSTITUTES.
MAYBE IT DOESN'T NEED TO BE
BIOIDENTICAL TO RECREATE THE
SAME EFFECT.
>> AND SOMEBODY WAS ALSO -- FOOD
SAFETY OBVIOUSLY NEEDS TO BE A
KEY CONSIDERATION IN ADVANCE OF
ANY BENEFITS THAT MAY BE PRESENT
BUT SAFETY IS CRITICAL.
KOTARO, FROM YOUR EARLIER
SESSION THERE HAD BEEN
OUTSTANDING QUESTIONS, I DON'T
KNOW IF YOU WANTED TO RAISE SOME
OF THOSE FROM BEFORE.
AND THEN ALSO THERE HAVE BEEN
SOME OTHER QUESTIONS THAT CAME
IN RELATED TO END POINTS.
DR. BODE HAS A QUESTION.
WAS IT RELATED ON THIS TOPIC,
LARS?
>> YEAH, MAYBE YOU WANT TO
HIGHLIGHT, JOE MENTIONED THE GOS
ADDED, COULD THEY HAVE AN
EFFECT, I WOULDN'T BE TOO
CONCERNED BECAUSE REALLY THE
WORKSHOP IS ABOUT SAFETY
EVALUATION.
I THINK THAT'S NOT DISCUSSED
MUCH AT ALL IS THERE IS REPORTS
THAT GOS CREATED ANAPHYLACTIC
REACTION IN SOME ASIAN
POPULATION, I'M NOT SURE THE
SPECIFIC COMPONENTS HAVE BEEN
CLEAVED OUT OF THE GOS OR NOT.
WHEN WE TALK ABOUT ALLERGIC
REACTION WE THINK ABOUT PROTEIN
BUT IT COULD BE SHORT CHAIN
OLIGOSACCHARIDE.
THIS IS SOMETHING TO REVISIT
THAT IF WE AIDE SOMETHING THAT'S
NOT IN HUMAN MILK, IT COULD
POTENTIALLY HAVE SIDE EFFECTS
THAT WE DON'T ANTICIPATE.
THEY ARE NOT SIMILAR TO HUMAN
MINIMUMMING BUT COULD DO SIMILAR
THINGS BUT COULD ADVERSE THINGS
WE'RE NOT CONSIDERING RING AT
THIS POINT.
>> WERE THERE KEY THINGS YOU
WANTED TO RAISE TO THE GROUP?
>> I DO WANT TO TOUCH ON WHAT
DAVID DALLAS BROUGHT UP, THIS
CONCEPT OF HOW MUCH IS ENOUGH,
HOW MUCH -- WE CERTAINLY DON'T
WANT TO DISCOURAGE INNOVATION,
THAT'S NOT THE INTENT OF FDA.
WE ENCOURAGE INNOVATION.
BUT THE DIFFICULTY HERE IS
TRYING TO GET A SENSE OF
BALANCE, SENSE OF WHAT ARE THE
TYPES OF DATA AND INFORMATION TO
GET TO SAFETY.
THIS IS WHY THIS WORKSHOP IS SO
IMPORTANT FOR US BECAUSE WE NEED
EVERYBODY TALKING.
INCLUDING CLINICIANS AND
RESEARCHERS TO CHIME IN ON THESE
THINGS.
AND ONE OF THE THINGS THAT I
THINK THAT WE SOMETIMES STRUGGLE
IS THIS IDEA IN TERMS OF
ENDPOINTS AND IN TERMS OF STUDY
DESIGNS, THINGS LIKE THAT, WHAT
ARE APPROPRIATE ONES, THAT'S AN
AREA THAT'S BEYOND WHAT WE WANT
TO ACCOMPLISH IN THIS WORKSHOP.
AS WE GO FORWARD WE DO NEED TO
THINK ABOUT WHETHER OR NOT WE'RE
LOOKING AT ALL THE ENDPOINTS
THAT WE NEED PARTICULARLY FOR
BIOACTIVES THAT MAY HAVE
SPECIFIC PHYSIOLOGICAL EFFECTS,
AND ARE WE LOOKING AT ENOUGH OF
THOSE ENDPOINTS, TO THE POINT
WE'RE PROPOSING WE SHOULD DO
100,000 STUDIES TO MAKE SURE
IT'S SAFE, I MEAN WE CERTAINLY
THAT'S NOT PLAUSIBLE.
AND SO THAT IS PART OF THE
CONVERSATION.
HOW MUCH IS ENOUGH?
WHAT TYPE OF THINGS WE NEED TO
LOOK AT.
I WANTED TO JUST EXPRESS THAT
FROM OUR END.
I APPRECIATE THE DISCUSSION AND
COMMENTS ON GETTING AT THIS
BECAUSE WE'RE CERTAINLY NOT HERE
TO IMPEDE INNOVATION, AS WE
SOMETIMES GET ACCUSED OF DOING.
WE DO WANT TO FOLLOW THE
SCIENCE.
I THINK, YOU KNOW, IT'S WITH SO
MUCH BEING REPORTED AND
PUBLISHED IT'S HARD TO GAIN
CONFIDENCE, AND WE TRYING TO
START THE CONVERSATION.
TO GET TO THIS IDEA OF DO WE --
ARE WE MAKING A BIG DEAL OUT OF
NOTHING, FOR EXAMPLE WE KNOW
THAT PROTEIN -- ONE OF THE
QUESTIONS ASKED EARLIER, WE KNOW
THERE ARE VARIATIONS IN PROTEIN
LEVELS, AND THE FACT THAT DOES
IT REALLY MATTER WHETHER WE SET
PARTICULAR PROTEIN LEVELS,
BECAUSE OBVIOUSLY INFANTS CAN
TOLERATE AND FIGURE OUT A WAY
TO, YOU KNOW, DEVELOP NORMALLY.
SO HOW MUCH DO WE NEED TO BE
CONCERNED ABOUT THOSE THINGS.
IT'S JUST NOT PROTEINS.
IT COULD BE ANYTHING THAT'S IN
HUMAN MILK.
AGAIN, THAT'S A QUESTION FOR
EVERYONE.
ARE WE OKAY WITH THIS CONCEPT
OF, WELL, IF IT'S IN HUMAN MILK,
WE SEE A BIG VARIATION DOES THAT
MEAN ANY OF THOSE LEVELS BELOW A
CERTAIN LEVEL IS CONSIDERED
OKAY?
IS THAT A SAFE ASSUMPTION?
ARE THERE EXPERIMENTAL EVIDENCES
TO COME TO THAT CONCLUSION?
AND MAYBE THE ANSWER IS YES.
AND MAYBE I'LL POSE THAT AS A
QUESTION, REASONABLE ASSUMPTION
TO MAKE?
DOES ANYBODY WANT TO CHIME IN ON
THAT?
>> I'LL MAKE ONE COMMENT.
IT'S REALLY NOT THE
CONCENTRATION IN MILK THAT'S
IMPORTANT.
IT'S THE DAILY INTAKE.
AND WE DON'T ALWAYS HAVE THAT.
THOSE VALUES.
SO, YOU KNOW, I DON'T KNOW.
I DON'T HAVE AN ANSWER TO YOUR
QUESTION, BUT IT HAS MORE TO DO
WITH THAT.
THE DATA THAT I SHOWED FROM THE
GLOBAL COHORTS IS VERY POSSIBLE
THAT THOSE COHORTS WHERE THE
PROTEIN CONCENTRATION WAS HIGHER
THAT THE INFANTS ARE CONSUMING
LESS MILK, LESS VOLUME.
WE DON'T KNOW.
I THINK WE HAVE TO BE CAREFUL
ABOUT THAT.
>> RIGHT.
I AGREE.
I THINK WE DO TEND TO FOCUS ON
LEVEL WITHOUT CONSIDERING THE
ACTUAL VOLUME THAT'S BEING
CONSUMED, PER FEEDING OR PER
DAY.
WE DON'T ALWAYS KIND OF PUT
THOSE TWO DATA TOGETHER TO
ACTUALLY GET A REAL GOOD SENSE
OF WHAT WE'RE SEEING HERE.
>> YEAH, IT'S ODD.
WE WOULD NEVER DO AN ADULT
DIETARY ASSESSMENT BY JUST
ASKING HOW MANY APPLES THEY ATE
OR WHAT WAS CONCENTRATION OF
VITAMIN C IN THE APPLE.
WE TAKE BOTH OF THOSE INDICES
AND MULTIPLY AND COME UP WITH
DAILY INTAKE.
>> WE DON'T DO THAT IN HUMAN
STUDIES BECAUSE IT'S HARD TO DO
BUT THAT'S THE ENDPOINT WE'RE
LOOKING AT.
>> GO AHEAD, SORRY.
>> I SAW LARS POSTED THE
PubMed FOR THAT UNFORTUNATE
OUTCOME.
WE HAD A QUESTION ABOUT -- I
DON'T KNOW, LARS, IF YOU'LL
HANDLE THIS TOMORROW.
BUT THERE SEEMS TO BE AN ISSUE
OF ABSENCE OF EVIDENCE OF ACTUAL
HARM, DOESN'T MEAN THERE'S NO
POSSIBILITY OF HARM, ESPECIALLY
WHEN THINGS COULD BE DOWN THE
ROAD IN TIME.
IT'S A VERY DIFFICULT PROBLEM.
AND I HOPE IT WILL BE ADDRESSED
BY SOMEONE.
>> YES, BACK TO THE REASONABLE
CERTAINTY OF NO HARM.
YES.
LARS, YOU JUST APPEARED.
>> MY NAME JUST POPPED UP.
I'M WORKING ON MY SLIDES RIGHT
NOW.
I'M LATE WITH MY SLIDES.
I HAVE THE FLEXIBILITY OF
CHANGING THINGS.
YOU'RE ABSOLUTELY RIGHT, NANCY.
WE'VE SHOWN THIS IN A POSITIVE
WAY THAT OLIGOSACCHARIDE
COMPOSITION AT ONE MONTH OF AGE
SOMEHOW PREDICTS COGNITIVE
OUTSOME AT TWO -- OUTCOME AT
TWO, AT SIX MONTHS IT DOESN'T
MATTER AT LEAST SPECIFIC
OUTCOMES, SEEMS TO BE SOMETHING
GOING ON, PRIMING OF WELL-BEING
IN GENERAL.
WE GOT A GRANT FUNDED LOOKING AT
INFANT MEETING AND LATER RISK
FOR ATHEROSCLEROSIS, IN THE
FIRST THEY WEEKS IN THE MOUSE
DRIVES IT WHEN IT GETS OLD, THAT
WOULD BE ONE OLIGOSACCHARIDE,
WE'RE TRYING TO SEE IF THAT
TRANSLATES TO HUMANS BUT THAT'S
NOT JUST BENEFIT, IT'S ALSO
QUESTION OF RISK AND SAFETY.
BUT HOW DO YOU REALLY STUDY
THAT, ESPECIALLY HOW DO YOU
STUDY IN HUMANS, YOU CAN'T WAIT
50 YEARS AND SEE IF THIS PERSON
HAS A HEART ATTACK OR NOT,
DEPENDING ON INTERVENTION.
IT'S A HUGE PROBLEM THAT IS NOT
EASILY ADDRESSED TO LOOK AT
LONG-TERM SAFETY OUTCOMES.
>> THANK YOU.
>> LARS, I WAS GOING TO ASK, NOT
JUST YOU, ANYONE ELSE, ARE THERE
ANY INDICATIONS THAT WE'RE
GETTING CLOSER TO IDENTIFYING
SPECIFIC BIOMARKERS OF ANY
PARTICULAR DEVELOPMENTAL OUTCOME
THAT COULD BE PREDICTABLE OF
LONG-TERM OUTCOME?
AND WE'RE TALKING ABOUT ANYTHING
FROM AMINO MARKERS, END
CONTRIBUTE -- ENDOCRINE MARKERS,
HOW CLOSE ARE WE COULD GETTING
BIOMARKERS THAT ARE NECESSARY TO
KIND OF FORESEE WHAT LONG-TERM
IMPACT MIGHT BE ON ANY
PARTICULAR ORGAN SYSTEM?
>> YEAH, I CAN ONLY SPEAK FOR
THE SPECIFIC ATHEROSCLEROSIS
PROJECT IN MELBOURNE, WORKING
WITH A GROUP, REALLY TRYING TO
IDENTIFY EARLY MARKERS OF
ATHEROSCLEROSIS IN INFANCY AND
CHILDHOOD, CAN PREDICT WHETHER
THAT LEADS TO ATHEROSCLEROSIS
LATER ON IN LIFE.
MAYBE YOU COULD SHORTEN THE
PERIOD OF YOUR OBSERVATION BY
LOOKING AT EARLY MARKERS AND HOW
INDIVIDUAL COMPONENTS CHANGE THE
EARLY MARKERS.
BUT THAT MIGHT BE VERY DIFFERENT
FOR OTHER DISEASE OUTCOMES, SO
THE ARRAY AND PANEL OF DIFFERENT
MARKERS, EARLY MARKERS OF
DISEASE OUTCOME LATER ON.
>> DAVID, GO AHEAD.
>> I LOVE THIS QUESTION.
I LOVE THAT WE HAVE ASSEMBLED
SUCH AN ESTEEMED GROUP TO HELP
US ANSWER BUT A LOT OF OUR --
NOT TO BE CHEEKY, A LOT OF
BIOMARKERS ARE MARKERS OF MOST
PREDICTED VALUE, SOCIAL MARKERS.
AND ALSO PSYCHOLOGICAL MARKERS.
IN TERMS OF SKIN TO SKIN CONTACT
AND QUALITY AND QUANTITY OF
INTERACTIONS BETWEEN INFANT AND
CAREGIVERS, ACCESS TO XYZ,
REGARDLESS OF WHO IS PROVIDING
THE BREAST MILK, DONOR OR
OTHERS, REGARDLESS OF WHO
DEVELOPS FORMULA, PRESENT, PAST,
FUTURE.
THIS IS NOT MY FIELD OF
EXPERTISE BUT THAT WAS THE MOST
COMPELLING EVIDENCE I'VE SEEN.
AGAIN, I KNOW IT'S NOT WHAT YOU
WERE ASKING DIRECTLY, BUT I'M
REALLY INTERESTED IN MOLECULAR
MARKERS AS WELL.
>> SHARING COMMENT, SO DIFFICULT
TO DO LIFE COURSE STUDIES, WHEN
WE LOOK AT LONG-TERM, KEEPING IN
MIND THAT FORMULA COMPOSITION
(INDISCERNIBLE) BREAST MILK
COMPOSITION IS A MOVING TARGET.
WHEE -- WE HAD A PERIOD OF TIME
INFANTS WERE EXPOSED FATTY ACIDS
IN BREAST MILK AND REMOVED, SOME
WAYS MIGHT BE ABLE TO GET TO
THIS THROUGH EPIDEMIOLOGY TO
LOOKING AT PERIODS OF TIME,
DRAMATIC CHANGES BUT TO ME THIS
QUESTION IS IT'S A SCREENING
WHERE WE NEED OMICS, AND I'M
REALLY FASCINATED BY THIS IDEA
OF AN INFANT'S SNPs OR
GENETICS, BECAUSE IN SOME WAYS
IT'S EASIER TO GET YOUR HANDS
AROUND THE MICROBIOME, WE CAN
BEGIN TO SEE -- SO MANY
CONFERENCES, I THINK OF THE
CONFERENCE, MEGAN, YOUR
COLLEAGUE THEY UNIVERSITY OF
TORONTO TALKING ABOUT ONLY IN
INFANTS WITH SPECIFIC GENETICS
MOST BENEFICIAL FOR PRODUCING I
THINK ASTHMA WAS THE OUTCOME.
I THINK THAT'S THE GRANULARITY,
THIS IDEA OF PERSONALIZED
NUTRITION, THAT WE'RE GETTING
TO.
STRUCK BY DAVID'S COMMENT
LOOKING AT METABOLITES, THE
MICROBIOME, SPECIFIC MICROBES
MIGHT BE MORE INFORMATIVE BUT I
THINK GETTING BACK TO THE IDEA
OF WE REALLY NEED A MODERN
COHORT THAT WE CAN VERY WELL
PHENOTYPE NOT ONLY THE INFANT
BUT THE MILK AND THE MOTHER AND
ALL THE SOCIAL DETERMINANTS OF
HEALTH THAT SURROUND THAT AND SO
SORT OF BEGIN THE MOONSHOT, YOU
KNOW, BUT I ALSO THINK THERE'S
POTENTIALLY LOW-HANGING FRUIT
OUT THERE, FROM EPIDEMIOLOGICAL
PERSPECTIVE, PERHAPS WE CAN
START TO GET TO.
THIS IS REALLY CHALLENGING AND
STUDIES NEED TO BE DONE BUT
STUDIES ARE GOING TO REQUIRE AN
INVESTMENT.
WHO IS INVESTING IS GOING TO BE
AN INTERESTING CONVERSATION.
I WAS STRUCK BY THE IDEA
POST-MARKET SURVEILLANCE, YOU
KNOW, THE COMMENT WE'VE HAD
(INDISCERNIBLE) FORMULAS FOR SO
LONG, FOR A PERIOD OF TIME, YOU
KNOW, THERE WAS A PRESENTATION,
A PUBLICATION FROM ONE OF THE
COMPANIES WHERE THEY WERE SORT
OF GETTING TO THAT, WE'VE ADDED
HMOs, HERE IS DATA ON
THOUSANDS OF INFANTS THAT HAD
THIS.
WE DON'T SEE ADVERSE EFFECTS BUT
THERE'S SOME BENEFIT.
LAST CONTINUE, THIS CONCEPT OF
SPRINKLING A LITTLE BIT IN THE
CAN SO YOU CAN SAY YOU HAVE IT,
WE'RE FACING THAT WITH HMOs,
THE LEVELS OF HMOs IN INFANT
FORMULAS ARE NOWHERE NEAR WHAT'S
IN HUMAN MILK.
AND SO IF WE'RE NOT SEEING
BENEFITS, MAYBE THERE'S NOT
ENOUGH THERE.
>> THIS IS JOE.
ONE OF THE THINGS THAT HAVE BEEN
TALKED ABOUT HERE ARE NUMEROUS
MOVING TARGETS IN HUMANS.
AND I THINK I BROUGHT IT UP IN
MY TALK.
WE MAY NOT BE COMPLETELY READY
FOR IT YET, BUT I THINK WE'RE
GETTING THERE.
WE ARE ABLE TO GET VOICE
RECOGNITION.
WE'RE ABLE TO RECOGNIZE FACES ON
CELL PHONES. WE HAVE A
SELF-DRIVING CARS.
I THINK THAT WITH SOME OF THESE
NEWER DEVELOPING TECHNOLOGIES IF
WE'RE ABLE TO PUT THOSE TOGETHER
WITH THE MULTI-OMICS TECHNIQUES
AND LOOK AT SEVERAL FEATURES,
OVERALL LONG TERM, I THINK THAT
WE SHOULD BE ABLE TO DEVELOP
SOME OF THESE BIOMARKERS THAT
KOTARO HAS BEEN TALKING ABOUT,
THE RISK BIOMARKERS, AND
INTERVENE EARLY ONCE WE HAVE
THESE RISK BIOMARKERS.
SOUNDS LIKE PIE IN THE SKY BUT,
YOU KNOW, I THINK WE MIGHT BE
GETTING THERE.
>> I THINK IT'S IMPORTANT THAT
WE THINK A LITTLE BIT WHETHER
THE FDA REGULATORY GUIDANCE
AROUND THE SPECIFIC EVALUATIONS
OF MAJOR CHANGES IN FORMULAS IS
AGAIN THE PARADIGM OF 50 YEARS,
BALANCE STUDY, PEOPLE TALK ABOUT
SEROVALUES, WE TALK ABOUT NOW,
JOE, A COMPLETELY DIFFERENT
LOOK.
WHAT WE'RE TALKING ABOUT IS
COMPLETELY DIFFERENT APPROACH TO
BOTH SAFETY AND EFFICACY AND I
THINK THAT RATHER THAN JUST
SIMPLE SHORT-TERM GUIDANCE MAYBE
THE FDA NEEDS STATUTORY
EVALUATION, A DIFFERENT WAY TO
LOOK AT SAFETY AND EFFICACY THAN
BEFORE
>> I WANTED TO FOLLOW UP ON WHAT
YOU WERE SAYING FROM SHARON,
THIS QUESTION OF INVESTMENT AND
WHERE DOES THE FUNDING COME FROM
TO DO ALL THIS RESEARCH.
I THINK IT'S -- YOU KNOW,
COMPANIES WHO ARE DEVELOPING
THESE NEW PRODUCTS LIKELY DON'T
HAVE THE RESOURCES TO INVEST,
TO, YOU KNOW, STUDY ALL THESE
DIFFERENT ENDPOINTS.
YOU KNOW, A LOT OF THIS WOULD
REQUIRE A VERY BIG TEAM-BASED
APPROACH TO INVESTIGATE MANY
ENDPOINTS.
HOW DOES THAT HAPPEN?
IS THAT LIKE GOVERNMENT/COMPANY
PARTNERSHIP?
OR WHAT?
I THINK IF WE RELY JUST ON THE
COMPANIES TO DO IT, WHICH IS HOW
I THINK THINGS ARE CURRENTLY
DONE WITH GETTING APPROVAL TO
ADD TO FORMULA I DON'T THINK WE
CAN EXPECT THEM TO DO ALL THAT.
>> I'D LIKE TO FOLLOW UP ON THAT
AS WELL.
THIS IS ALSO IN RESPONSE TO
SHARON.
AND THIS IDEA OF THE MOONSHOT
STUDY, WHO WILL FUND IT, THIS IS
ALL ONE BIG CONVERSATION.
THERE'S SEVERAL OF US THAT HAVE
BEEN ADVOCATING FOR SOME SORT OF
HUMAN MILK PROJECT LIKE THE
HUMAN GENOME PROJECT LIKE THE
HUMAN MICROBIOME PROJECT, FOR
YEARS.
TEAM SCIENCE APPROACH WHERE WE
DO LOOK AT EVERYTHING IN MILK
AND DO THE MULTI-OMICS AND DO
HAVE MULTIPLE COHORTS.
AND WE POOL OUR EXPERTISE
BECAUSE DIFFERENT LABS DO
DIFFERENT THINGS WELL.
AND I THINK IT'S GOING TO TAKE A
GROUP EFFORT LIKE THAT.
I REALLY DO.
IT'S A BIG PROJECT BUT ONCE
AGAIN THERE'S NO OTHER FOOD
THAT'S MORE IMPORTANT TO
UNDERSTAND, HAS IMPLICATION
DIRECTLY TO HUMAN HEALTH AND FOR
APPLICATIONS LIKE INFANT
FORMULA.
SO I WOULD LOVE TO SEE SOME
PUBLIC/PRIVATE PARTNERSHIP LIKE
THAT.
>> JUST NOTICING THAT MEGAN, YOU
HAD POPPED UP.
DID YOU WANT TO CHIME IN ON
SOMETHING, TO THIS POINT OR
SOMETHING THAT WAS MADE EARLIER.
>> NOTHING IN PARTICULAR.
I JUST HEARD MY NAME MENTIONED,
I WANTED TO NOD ALONG.
THIS IS A GOOD PLACE TO JUMP IN.
I DEFINITELY AGREE.
SO LEADING AN INTERNATIONAL
PROJECT, SOME OF ARE YOU
PARTNERS ON, INCLUDING SHELLEY,
LOOKING AT MILK COMPOSITION IN A
COMPREHENSIVE WAY FUNDED BY THE
BILL AND MELINDA GATES
FOUNDATION, TEAM-BASED PROJECTS,
WE'VE ENGAGED PEOPLE EXPERTS IN
DIFFERENT DOMAINS, ENGAGED DATA
SCIENTISTS, THAT'S THE
TEAM-BASED APPROACH, I FULLY
SUPPORT WHAT SHELLEY PROPOSED.
I LIKE WHAT SHARON WAS SAYING,
I'M ON HER WORKING GROUP FOR THE
BEGIN PROJECT, ABOUT A MOONSHOT
PROJECT, CHARACTERIZING NOT ONLY
MILK BUT OTHER INPUTS INTO IT.
INFANTS, MOTHERS, THE
ENVIRONMENT.
AND THEN HAVING SUSTAINED
LONG-TERM FUNDING TO FOLLOW UP
INFANTS NOT JUST FOR A FEW
MONTHS TO SEE HOW THEY GROW, BUT
LATER ON TO LOOK AT SOME OF
THESE LONGER-TERM OUTCOMES, SOME
OF THOSE WE DON'T HAVE TO WAIT
UNTIL THEY ARE ADULTS BUT COULD
GET BIOMARKERS OF CHRONIC
DISEASE AND THAT WOULD BE REALLY
INFORMATIVE SO STUDIES LIKE
(INDISCERNIBLE) AND WE'RE
FORTUNATE THERE'S MILK THERE TO
STUDY BUT NEVER DESIGNED AS A
MULLING STUD -- MILK STUDY SO
THERE ARE LIMITATIONS, DESIGNING
TRUE MILK STUDIES FROM TEAM
BASED APPROACH IS WHERE WE NEED
TO GO.
>> TEAM SCIENCE ALL THE WAY.
>> WE'RE NEARING THE END OF OUR
TIME WHICH HAS FLOWN BY.
BEFORE WE MOVE TOWARDS THAT,
JOE, DID YOU WANT TO SAY
SOMETHING?
I NOTICED YOU CAME OFF MUTE.
NO?
OR SHARON ALSO, JUST WANT TO
CHECK.
SO I'M CHECKING WITH SHARON,
LOOKING AROUND THE VIRTUAL ROOM
HERE.
SO WONDERFUL WITH THIS
TECHNOLOGY.
GO AHEAD.
>> I WAS GOING TO ADD TO WHAT
MEGAN AND SHELLY COMMENTED ON,
IN ADDITION TO HAVING A LARGE
STUDY, ONE OF THE LIMITATIONS
BROUGHT UP IS GRIs, FOR
INFANTS, SO MANY ARE
EXTRAPOLATED, SO BETWEEN --
RECENT NATIONAL COMPANIES
REPORTS, SEVERAL PEOPLE SERVED
ON, DIETARY GUIDELINES, THERE'S
REAL BEEN -- WE NEED TO INVEST
IN UNDERSTANDING REQUIREMENTS OF
INFANTS, WHICH IS FUNDAMENTAL,
AND HUMAN MILK COMPOSITION, ALL
ITS VARIABILITY BECAUSE A LOT OF
WHAT WE'RE BASING IT ON, PART OF
THE DATA CAME FROM THE LAST
MAJOR INVESTMENT IN NIH,
COMPOSITION, FROM THE '70s.
AND SO, YOU KNOW, I AGREE 100%
THIS IS A FUNDAMENTAL TIME IN
DEVELOPMENT, WHAT WE KNOW IS
THIS TRAJECTORY OF HEALTH IS SET
DURING THIS PERIOD OF TIME.
AND I'M SPEAKING ABOUT A COMMENT
EARLIER THAT WAS MADE THAT IN
RESPONSE TO SHELLEY IF THERE'S
NO DRI FOR IT BE IN FORMULA?
WELL, BUT THAT'S THE WHOLE --
MANY OF US THINK ABOUT THE WHOLE
ADVANTAGE OF HUMAN MILK IS THAT
IT'S NOT JUST NUTRIENTS AND
THERE'S SO MANY FOODS THAT HAVE
HEALTH BENEFITS THAT ARE WELL
BEYOND OUR CLASSIC UNDERSTANDING
OF NUTRIENTS, SO WE NEED TO
UNDERSTAND.
IT'S FUNDAMENTAL TO
UNDERSTANDING HOW WE MAKE INFANT
FORMULAS, THAT THE MAGIC OF
HUMAN MILK ALL THESE THINGS IT
CAN DO BEYOND.
I THINK THE COMMENT ABOUT THE
MULTI-FUNCTIONALITY OF
INGREDIENTS AND A SINGLE
COMPONENT CAN HAVE MULTIPLE
FUNCTIONS AND STUDIES, DIGESTED
INTO PEPTIDES, THOSE CAN HAVE
FUNCTIONALITY, SO I THINK OUR
HASHTAG #SHOULD BE WE DON'T
KNOW.
WE DON'T KNOW BECAUSE THERE'S
NOT SYSTEMATIC INVESTMENT IN
RESEARCH IN THIS AGE GROUP.
SO IF WE WANT TO STOP SAYING WE
DON'T KNOW, WE NEED TO FUND
RESEARCH.
>> RIGHT.
AND I THINK THAT'S A GREAT POINT
MAYBE TO WRAP THINGS UP ON,
SHARON.
JUST TO ADD A LITTLE MORE TO
YOUR POINT, THAT THAT'S PART OF
THE PURPOSE FOR THE WORKSHOP, TO
IDENTIFY KEY THINGS WE DON'T
KNOW AND PUSH EVERYBODY A LITTLE
BIT TO SEE WHAT -- BEYOND WHAT
IS KNOWN AND WHAT DO YOU THINK,
AND TO EXTEND A LITTLE MORE SOME
OF THE KEY AREAS.
SO THANK YOU, EVERYBODY.
I FEEL LIKE WE'VE DONE THAT.
AND WE'LL CONTINUE TO DO THAT.
AND SO A VERY BIG THANKS TO ALL
OF OUR SPEAKERS TODAY.
AND SO I'LL GO AHEAD AND THANK
EVERYBODY AND PASS BACK TO
ASHLEY.
>> THANK YOU, ROBIN.
THANK YOU, MODERATORS AND
SPEAKERS, FOR A FABULOUS SESSION
TODAY.
TODAY WE RAN THROUGH EVERYTHING
FROM NORMAL INFANT DEVELOPMENT
IN MULTIPLE MAJOR FIELDS OF
STUDY TO HUMAN MILK WHICH IS ITS
OWN ENTIRE FIELD OF RESEARCH.
WE ALSO BEGAN THE CONVERSATION
ON TECHNICAL CONSIDERATIONS FOR
BIOACTIVE INGREDIENTS AND INFANT
FORMULA AND DID ALL OF THIS IN A
FEW HOURS.
SO I REALLY WANT TO SAY KUDOS TO
OUR SPEAKERS WHO WERE ABLE TO
DISTILL AND TRANSFER A RICH
AMOUNT OF INFORMATION IN A VERY
SHORT AMOUNT OF TIME ON TOP OF
ANSWERING DIFFICULT QUESTIONS
WHICH SOMETIMES TURNED INTO A
HASHTAG #WE DON'T KNOW, WHICH IS
FINE.
ONE TAKEHOME THAT STUCK ME WAS
THE POINT PUTTING THE CART
BEFORE THE HORSE, WE'RE STILL
LEARNING ABOUT FUNCTION OF
BIOACTIVES IN HUMAN MILK.
LET ALONE THEIR FUNCTION IN
INFANT FORMULA.
I THINK THE SPEAKERS AND
MODERATORS ALL RECOGNIZE THERE'S
A PRACTICAL NEED BY RESEARCHERS,
FUNDERS, CLINICIANS, FOOD
SCIENTISTS, TECHNOLOGISTS,
REGULATORS, PROBABLY MISSING
PEOPLE IN THE LIST, TO DETERMINE
WHEN WE KNOW ENOUGH TO MOVE
FORWARD IN THEIR PARTICULAR AREA
OF WORK.
SO ONE SOLUTION TO THIS THAT WAS
BROUGHT UP THAT I THOUGHT WAS
PARTICULARLY PERTINENT WAS NEED
FOR TEAM SCIENCE AND NEED TO
REALLY THINK ABOUT THIS AS A
BIOLOGICAL SYSTEM.
AS WE CLOSE TODAY, I HAVE A
COUPLE QUESTIONS I WANT TO LEAVE
PEOPLE WITH TO THINK ABOUT.
FIRST IS GIVEN LIMITED RESOURCES
AND TIME WHAT IS THE MOST
IMPORTANT INFANT HEALTH AND
DEVELOPMENTAL OUTCOME TO THINK
ABOUT AT THIS MOMENT?
WHERE DO WE NEED TO SPEND MONEY,
EFFORTS, TIME, YOUR BRAINPOWER,
MOVING FORWARD?
WHAT IS THE KEY THING AT THIS
MOMENT?
AND THEN WHEN YOU SEE THE CAN OR
BOTTLE OF INFANT FORMULA WHAT DO
YOU GET EXCITED ABOUT?
WHAT SCIENCE GETS YOU EXCITED
WHEN YOU SEE THAT?
THINKING ABOUT WHAT NEEDS TO BE
DONE RIGHT NOW IS VERY
IMPORTANT, ALSO CURIOUS TO THINK
ABOUT WHAT ARE SOME EXCITING
THINGS ON THE HORIZON AND SO WE
HAVE A FULL DAY TOMORROW WHERE
WE'RE GOING TO START AGAIN WITH
SCIENTIFIC SESSIONS AND THEN
HAVE SOME TIME, A COUPLE HOURS
TO DIVE INTO DEEPER DISCUSSIONS.
WE THANK OUR ATTENDEES, AGAIN
SPEAKERS AND MODERATORS, AND
RECONVENE TOMORROW AT 10:30 A.M.
EASTERN STANDARD TIME, AND FOR
THOSE IN EASTERN TIME I WILL
TELL YOU TO HAVE A LOVELY
EVENING.
THANKS SO MUCH.