Documente Academic
Documente Profesional
Documente Cultură
MICROBIOME PROGRAM
Theroleofdiets:Standardizationand
characterization
GaryD.Wu,M.D.
FerdinandG.Weisbrod ProfessorofMedicine
DivisionofGastroenterology
PerelmanSchoolofMedicine
UniversityofPennsylvania
Agenda
Functional impact diet on the murine gut microbiota and its
metabolome
Diet,theGutMicrobiome,anditsMetabolome
Holmesetal.CellMet.2012;16:559
EffectofDietonComposition oftheGut
Microbiota anditsImpactonDisease
SartorRB.Nat.Rev.Gastro.andHep.2012
EffectofDietonMetaboliteProductionbythe
GutMicrobiota anditsImpactonDisease
Wangetal.Nature.2011;472:5763
IncidenceofIBDIncreasingWorldwide
CD
NA&
Europe
(70s80s)
UC
Asia
(2000s)
DefinedFormulaDietsandtheTreatment
ofCrohns Disease
ResponsetoDietaryTherapy
Elemental
Nonelemental
Giaffer,1990
Kobayashi,1998
Mansfield,1995
Middleton,1995
Park,1991
Raouf,1991
Rigaud,1991
Royall,1994
Verma,2000
Sakurai,2002
100
80
60
40
20
0
TheRelationshipBetweenDiet,theGutMicrobiota,andIBD
Albenberg etal.CurrentOpinionGastro.2012
DefinedformuladietsforthetreatmentofCrohns diseasearethemost
effectivewhenconsumedcompletelyinplaceofanormaldiet(Exclusive
EnteralNutritionEEN).
DoesEENprovidesomethinggoodforpatientswithIBDthatisnotabundantin
theregulardiet?
DoestheconsumptionofEENexcludesomethingthatisbadforpatientswithIBD
intheregulardiet?
Agenda
Functional impact diet on the murine gut microbiota and its
metabolome
Agenda
Functional impact diet on the murine gut microbiota and its
metabolome
Agenda
Functional impact diet on the murine gut microbiota and its
metabolome
HostGutMicrobiota CoMetabolisminRodentModelSystems
Agenda
Functional impact diet on the murine gut microbiota and its
metabolome
PlasmaMetabolomics andtheGut
Microbiota inVegansandOmnivores
Crosssectionalstudy
15vegansand16omnivores
Three24hourdietaryrecallspriortosample
collection
Fastingplasma,urine,andstoolfor
metabolomics
Stoolforassessmentofmicrobiota composition
DietaryComposition
BetweenOmnivores
vs.Vegans
Wuetal.Gut2014
ThePlasmaandUrinary
Metabolome of
Omnivoresvs.Vegans
RandomForrest
UrinaryMetabolome
Bothdietandthe
plasma/urinarymetabolome
aredramaticallydifferent
betweenomnivoresandvegan.
Wuetal.Gut2014
ComparingtheCompositionoftheGutMicrobiota in
Vegansvs.Omnivores
ControlledFeedingExperiment:CAF
Wuetal.Science 2011;334:1058
Wuetal.Gut2014
10Healthyvolunteers
Randomizedtohighfibervs.lowfiberdiet
10dayinpatientstaywithsamemealseachday
Caloricintakeadjustedtomaintaincurrentweight
Dailystoolsamplecollection
Definedenvironmentalconditions
Definedgenetics
Monotonousdiet
Highsignaltonoiseratio
Freelivinginahighlyvariable
environment
Geneticdiversity
Variablediet
Lowsignaltonoiseratio
BUT
Proofofconceptcauseandeffect
relationshipsinamodestsizedcohort
Smalleffectsizesoverlarge
populationscanbehighlyimpactful
Examples(FDAdrugdevelopment
paradigmandfoodadditives)
AnimalWelfare
Limitedabilitytoexcludethetransferofmicrobiota via
coprophagia betweencohousedmice:
Environmentalstresswiththeusewirebottomcages
Socialisolationofindividuallyhousedmice
Impactoflongtermdietaryinterventionsinvolvingextreme
dietarymodificationsincompositionand/orcaloricintake
ImpactonhostphysiologywiththeintroductionofGRASfood
additivesintochowathighconcentrations
PennIntestinalMicrobiome ProjectGroup
Patient/subjectrecruitmentand
phenotyping,dietaryassessment,
samplecollectionandprocessing
RobertBaldassano,MD(CHOP)
*JamesD.Lewis,MD(Penn)
DNAsequencing,dataanalysis,and
mathematicalmodeling
*FredericD.Bushman,PhD(Penn)
Hongzhe Li,PhD(Penn)
KyleBittinger,PhD(CHOP)
Yun Li(Penn)
*GaryD.Wu,MD(Penn)
Microbiology
MarkGoulian,PhD(Penn)
GaryL.Lichtenstein,MD(Penn)
CharleneCompher,PhD,RD(Penn)
BiologicalOxymetry
SergeiVinogradov,PhD(Penn)
Metabolomics
MichaelBennett,PhD(CHOP)
MarcYudkoff,MD(CHOP)
*CoPrincipalInvestigators
JunChen,SamMinot,SerenaDollive,EricChen,ChristianHoffmann,YingYuChen,KyleBittinger,Jennifer
Hwang,ErinGilroy,Kernika Gupta,LisaNessel,LindseyAlbenberg,JudithKelsen,ColleenJudge,Christel
Chehoud,DavidShen,Rohini Sinha,DavidMetz,TatianaEsipova,SusanParrott,ElliotFriedman,JosieNi,
SarahSmith,LillianChau,EricaPanfen,AndrewLin,SarahSmith,JackJiang
PennCHOP
MICROBIOME PROGRAM
TheJointPennCHOPCenterfor
Digestive,Liver,andPancreaticMedicine
CenterforMolecularStudiesin
DigestiveandLiverDiseases
(P30DK050306)