Demystifying Microbiome Research: New Opportunities for ... · The human microbiota The term microbiota refers to the microbial populaon present within the human body, including bacteria,

Produced by

Demystifying Microbiome Research: New Opportunities for Health & Business

Antoine Bily Naturex

Matthew Roberts KGK Science

Francine Schoenwetter New Hope Network

KGK Science Inc. www.kgkscience.com Confidential © Copyright. All rights reserved

Demystifying Microbiome Research: New Opportunities for

Health & Business

Matthew Roberts Ph.D. M.B.A Chief Scientific Officer


Agenda•  WhatistheMicrobiome?•  AdvancesinMicrobiomeResearch•  RelevantEndpointsforMicrobiomeStudies

•  ClinicalSubstan=a=onofProbio=cs

•  ConcludingRemarks


Microbiome–Defini=on•  WhatweknowasthemicrobiomewascoinedbyJoshuaLederbergasa

meansto“signifytheecologicalcommunityofcommensal,symbio3c,andpathogenicmicro-organismsthatliterallyshareourbodyspaceandhavebeenallbutignoredasdeterminantsofhealthanddisease”(1)

•  Thetermmicrobiotaisthespecificmicrobialpopula=oninourbody

(bacteria,viruses,archea,protozoans,andfungi)

•  Themicrobiomeisviewedasthecatalogofthesemicrobesgenome(i.e.genes)(2)


Microbiome–History&Func=on•  Inves=ga=onofthediversityofthemicrobiomebeganasearlyasthe1680’s

whenAntonievanLeewenhoekcomparedhisoralandfecalmicrobiota,no=ngthattherewerestrikingdifferencesbetweenthe2samples(3)

•  Themutuallybeneficialrela=onshipbetweenvertebratesandmicrobeshas

evolvedovermillionsofyearsandthesemicro-organismshaveselectedforspecializedareasofourbodysuchasthegut,mouth,andskin

•  Approximately90%ofthecellsinourbodyaremadeupofthemicrobesthatcolonizeourgut.

•  Thegutmicrobiomecommunitycaninfluencemanyaspectsofourphysiologysuchasthemetabolism/absorp=onofnutrients,aswellasplayapreventa=veroleinthepathogenesisofvariousdiseases

Grenhametal.,2011


AdvancesinMicrobiomeResearchNutri=onanddietarysupplementscanimpactthegutmicrobiome.Thusresearchintotherela=onshipbetweenourgutmicrobiota,ourphysiology,anddietarysupplementshasbecomemorewidespread.Notableadvancesinclude;•  Hilderbrandtetal2009.,supplyingmicewithahigh-fatdietledtodecreased

BacteroidetesandincreasedFirmicutesandProteobacteriainthemurinegut,andthiswasindependentofweightgain

•  Sela&Mills2010.,thebioac=vemoleculesdissolvedinbreast-milkinfluencesthe

developmentofaninfantsgutmicrobiota.•  SmithMetal2013.,severelymalnourishedchildrenhavederegulatedgutmicrobiotathat

makeitdifficulttou=lizenutrientsfromfood.


AdvancesinMicrobiomeResearchOurgutmicrobiomemayalsoplayaroleinmetabolismandapersonalizedapproachtomedicine;•  TurnbaughPetal2009.,ourmetabolismhasbeenassociatedwithacoregut

microbiomeanddevia=onsfromthiscoreassemblyofmicrobiotaislinkedwithdifferentphysiologicalstates(i.e.obesevs.leanindividuals)

•  Knightetal2015.,crowd-fundedprojects,suchastheAmericanGut(par=cipantshavetheirmicrobiomessequenced)mayhelpreplenishourancestralmicrobesand/ordiscovernewonesthatwillhelpmaintainwellness

•  KnightRetal2016.,developmentofa“personalized”mousemodelsthatcan

harboranindividual’smicrobiomesotheeffectsofinterven=ons(nutrientsordrugs)canbetested


Psychobio=cs:ThemicrobiomeandtheGut-BrainAxis•  Messaoudietal2011.,L.helve=cusandB.longumreduced

psychologicaldistress

•  Steenbergenetal2015.,mul=-speciesprobio=creducednega=vethoughtsassociatedwithsadmood

•  Schmidtetal2015.,prebio=creducedstressresponseandincreasedprocessingofposi=vevs.nega=veajen=onalvigilance

•  Allenetal2016.,B.longumreducedselfreportedstressandimprovedbrainac=vity

•  Kato-Kataokaetal2017.,L.CaseistrainShirotareducedphysiologicalandphysicalsymptomsofstress

•  SampsonTetal2016.,amousewiththemicrobiotafrompa=entssufferingfromParkinson’sdevelopedthesamediseaseprogression

El-Ansaryetal2013


OralMicrobiomeResearch•  Parahi3yawaNB,etal.2010.Over6billionbacteria

spanningover700speciesinhabitthemouth

•  HealthCanada,2008.Oralhealthlinkedtooverallhealth(cardiovascular;diabetes;etc)

•  JamesKM,etal.2016.Specificprobio=ccombina=onspreventC.albicansbiofilmforma=onbydownregula=nggenescri=caltopathogenesis

•  KolipD,etal.2016.Dentaq®OralandENTHealthProbio=cComplexreducesgingivalinflamma=onandplaqueforma=oninadolescentorthodon=cpa=ents

Gingivi9s-P.gingivalis

GUMHEALTH

GENERALORALHEALTHOralCandidiasis-C.albicans

DentalCaries-S.mutans

TOOTHHEALTH


RelevantEndpointsforMicrobiomeStudies•  Collectmetagenomicdatafrommicrobiomescreening(QIIME,16SrRNA,

shotgungenomicanalysis).Thiscanbedoneinindividualsviafecalcollec=onandsubsequentextrac=onofRNA/DNAsequences(7)

•  Employtheuseofnovelbioinforma=ctools(e.g.,InnateDBandNetWorkAnalyst)toevaluatetheinterac=onofgenes,proteins,andcytokinesthatmaybemodulatedbyaltera=onstothemicrobiome(8)

•  Molecularmarkersofgastricemptying(viaradiopaquemarkers),GI

inflamma=on(fecalcalprotec=norlactoferrine),andmicrobiomestability(i.e.microbiomesequencebefore/aferaroundofan=bio=cs)(15)

•  Validatedgut-healthques=onnaires(bowlhabits,GIsymptoms,andqualityoflife)


ClinicalSubstan=a=onofProbio=csTheKGKAugmentedRandomizedControlledTrial:•  StudyDesign:trialdesignthatfollowsatwostageprocess

v  Stage1:Capturevaluableinforma=onastoop=malinclusioncriteria,dosing,andresponders

•  Meta-analysisofseveralN-of-1trialsv  Stage2:Confirmatorytrial,u=lizesinforma=ongatheredfromstage1toprovide

op=malInclusioncriteriainaRandomizeddouble-blindstudyOtherpointstoconsider:•  Endpoints:Diseaseendpointsthatrelatetodrugscommonlyused

v  KGKproposesdevelopmentofaglobalhealthindexforprobio=cs

•  Popula9on:Challengeofrecrui=nghealthypopula=onswithsufficientlylowintake


Summary•  Themicrobiomeisthecatalogofallthemicrobesandtheir

respec=vegenesthatcolonizeourgut(andotherareasofthebody)

•  Dietandsupplementscansignificantlyimpactthecomposi=on

ofthemicrobiomeandmaybeusedtoop=mizeitsfunc=on

•  Ahealthymicrobiomeiscri=caltomaintainwellnessandmaycontributetothepreven=onofchroniccondi=ons

•  Clinicalsubsta=onofsupplementsthatsupporthealthandwellnesswillcon=nuetobeofgreatimportance


AboutKGKFounded in 1997 and built on a foundation of scientific excellence, KGK is the leading contract research organization in the Nutraceutical Industry. Working to substantiate claims of dietary supplements, functional foods, and other natural health products, KGK incorporates the highest quality standards and state-of-the-art scientific technique and technologies to satisfy our client needs. With clinics in Canada and the USA, KGK Clinical Trial Centers can efficiently develop and manage your research throughout North America. KGK is renowned internationally for our ethical and specialized study of natural health products


References•  [1]LederbergJ&McCrayAT.’Omesweet’omics—agenealogicaltreasuryofwords.Scien=st.

2001;15:8.•  [2]UrsellL,MetcalfJ,ParfreyLW,&KnightR.DefiningtheHumanMicrobiome.NutrRev.2012;70:1.•  [3]vanLeeuwenhoekA.AnabstractofalejerfromAntonievanLeeuwenhoek,Sep12,1683.About

animalsinthescrurfoftheteeth.PhilosophicalTransac=onsoftheRoyalSocietyofLondon.1684;15:568.

•  [4]SelaD&MillsD.Nursingourmicrobiota:molecularlinkagesbetweenbifidobacteriaandmilkoligosaccharides.TrendsinMicrobiology.2010;18:7.

•  [5]SmithMetal.GutmicrobiomesofMalawiantwinpairsdiscordantforKwashiorkor.Scinece.2013;339:6119.

•  [6]Hilderbrandtetal.High-fatdietdeterminesthecomposi=onofthemurinegutmicrobiomeindependentlyofobesity.Gastroenterology.2009;137:5.

•  [7]TurnbaughPetal.Acoregutmicrobiomeinobeseandleantwins.Nature.2009;457:480.•  [8]KnightR.Knightlabresearch.UniversityofCalifornia.2016•  [9]KnightR.Microbiomeresearchmaysoonpayoffbig.Scien=ficAmerican.


References•  [10]MessaoudiMetal.Assessmentofpsychotropic-likeproper=esofaprobio=cformula=on(Lactobacillus

helve=cusR0052andBifidobacteriumlongumR0175)inratsandhumansubjects.BrJNutr.2011;105:755-64.

•  [11]SteenbergenL,SellaroR,vanHS,BoschJA,ColzatoLS.Arandomizedcontrolledtrialtotesttheeffectofmul=speciesprobio=csoncogni=vereac=vitytosadmood.BrainBehavImmun.2015;48:258-64.

•  [12]SchmidtK,CowenPJ,HarmerCJ,TzortzisG,ErringtonS,BurnetPW.Prebio=cintakereducesthewakingcor=solresponseandaltersemo=onalbiasinhealthyvolunteers.Psychopharmacology(Berl).2015;232:1793-801.

•  [13]AllenAP,HutchW,BorreYEetal.Bifidobacteriumlongum1714asatransla=onalpsychobio=c:modula=onofstress,electrophysiologyandneurocogni=oninhealthyvolunteers.TranslPsychiatry.2016;6:e939.

•  [14]Kato-KataokaA,NishidaK,TakadaMetal.FermentedmilkcontainingLactobacilluscaseistrainShirotapreventstheonsetofphysicalsymptomsinmedicalstudentsunderacademicexamina=onstress.BenefMicrobes.2016;7:153-6.

•  [15]Backhedetal.Definingahealthyhumangutmicrobiome:currentconcepts,futuredirec=ons,andclinicalapplica=ons.CellHost&Microbe.2012;12:5.

•  [16]Blumbergetal.Evidence-basedcriteriainthenutri=onalcontext.Nutri=onReviews.2010.68;8:478-484.


References•  [17]Gibsonetal.TheDesignofProbio=cStudiestoSubstan=ateHealthClaims.GutMicrobes.

2011:5;2:299-305.•  [18]Heaney,R.P.Nutrients,Endpoints,andtheProblemofProof.TheJournalofNutri=on.

2008:138;1591-1595.•  [19]Heaneyetal.EBN(Evidence-BasedNutri=on)Ver2.0.Nutri=onToday.2011:46;1.•  [20]Heaney,R.P.TheNutrientProblem.Nutri=onReviews.2012;70:3.•  [21]Heaney,R.P.Guidelinesforop=mizingdesignandanalysisofclinicalstudiesofnutrienteffects.

Nutri=onReviews.2014;72:1.•  [22]Nuzzo,R.Sta=s=calErrors:P-values,thegoldstandardofsta=s=calvalidity,arenotasreliableas

manyscien=stsassume.Nature.2014:506.•  [23]Poonetal.SearchingforEvidenceinTradi=onalChineseMedicineResearch:AReviewandNew

Opportuni=es.DataAnaly=csforTradi=onalChineseMedicineResearch.2014:1-16.•  [24]Shaneetal.Guidetodesigning,conduc=ng,publishingandcommunica=ngresultsofclinical

studiesinvolvingprobio=capplica=onsinhumanpar=cipants.GutMicrobes.2010:4;1.


References•  [25]Parahi=yawaetal.Exploringtheoralbacterialflora:currentstatusandfuturedirec=ons.2010:16.•  [26]JamesKMetal.Inhibi=onofCandidaalbicansbiofilmforma=onandmodula=onofgene

expressionbyprobio=ccellsandsupernatant.2016:65;4.•  [27]KolipDetal.Dentaq®OralandENTHealthProbio=cComplexreducesgingivalinflamma=onand

plaqueforma=oninadolescentorthodon=cpa=ents.2016•  [28]MinisterofHealth,HealthCanada.TheEffectsofOralHealthonOverallHealth.August2008.

How botanicals can benefit the gut

microbiota and its host?

Antoine Bily, Pascale Fança-Berthon

Demystifying microbiome research:

new opportunities for health & business Engredea, Thursday March 9th 2017

ThehumanmicrobiotaThe term microbiota refers to the microbialpopu l a=on p r e sen t w i t h i n t he humanbody, including bacteria, viruses, archea,protozoans,andfungiRepresents109mesmore cells thanhuman cells:1-2kgofmaterial

1014Microorganismsinthegut

Gutmicrobiota genome =microbiome =100 to 150 =mes more genes than ourowngenomeIt is a hottopic

Whatareitsfundamentalcharacteris=cs?Itisunique1000 species es=mated to bepartofthehumanmicrobiotaBut only 200 species perindividual ; each combina=onofspeciesisunique

Butfunc9onalac9vi9esofthemicrobiotaverysimilarfromahealthysubjecttoanother

It is possible to classify people according totheirenterotypei.e.,therela9veabundanceof3bacterialgroups:Bacteroides,PrevotellaandRuminococcus

Arumugam,Raesetal.Nature,2011

Whatareitsmainroles?The whole community of gut microbiota serves manyfunc=ons:

Grenhametal.FrontPhysiol,2011

What is dysbiosis?

Dysbiosisdefini=onDuringhealthy,homeosta=ccondi=onsthemicrobiota is composed of a diversity oforganism. However, environmental factorscan lead to altera=ons of the ecologicorganiza=onofthegutmicrobiotavia:-Pathobiontexpansion-Reduceddiversity-Lossofbeneficialmicrobes

PetersenandRound.CellularMicrobiology,2014Sergeyatal.NatureReviewsGastroenterology&Hepatology,2013

Thisisdysbiosis,aswitchfroma

mutualis9cbeneficialrela9onshiptoa

pathologicalunbeneficialrela9onship:

Obesity-relateddysbiosisandIR&steatosis

LossofdiversityPathobiontexpansion

Lossofbeneficialmicrobes

Leakygut–hypermeability

Lowgradeinflamma9on

Adipose3ssueMuscleLiver

Alteredglucose&lipidmetabolismSteatosis

Cani.NatRevEndocrinol.2014

Howcanwereversedysbiosis?

Probio=cs are “livemicro-organisms which, whenadministered in adequate amounts,conferahealthbenefitonthehost“

(Defini=onFAO/WHO2012)

Prebio=csare“selec=velyfermentedingredientsthatpromotetheselec=ves=mula=onofgrowthand/orac=vi=esofoneoralimitednumberofmicrobialgenus(era)/speciesinthegutmicrobiotathatconfer(s)healthbenefitstothehost”(Defini=onfromGibson&Roberfroidetal,2010)

Symbio=cs

REBIOSIS:Establishingamicrobial

communitybacktoahealthystatePostbio=cs are “non-

viable bacterial products ormetabol ic byproducts fromprobio=c microorganisms thathavebiologicac=vityinthehost”(Defini=onPatel&Dening,2013)

Botanicals?

Positive influence of a Fraxinus extract on

steatosis via gut microbiota modulation

WhatisFraxinusangus3folia?•  Fraxinusangus3foliaisatreeusuallyreferredtoas

narrow-leavedash

•  Historically,FraxinuswaslargelylimitedtotheMediterraneanBasin,wherelocalpopula=onsuseditinfoodandinfusions,andforitshypoglycemiceffect1

•  Glucevia®isanextractderivedexclusivelyfromthesamaraofFraxinusangus3folia

(1) Eddouks & Maghrani (2004) J. Ethnopharmacol.,94:149-154

ProductDescrip9on:PurifiedextractofFraxinussamaraStandardiza9on:>10%NuzhenideandGL3(=secoiridoids)viaHPLCSubstan9a9on:Clinicallyshowntoreducebloodglucose.ShowntoreducesteatosisinInvivoanimalmodels

MetabolicsyndromeandLiverHealth

hjp://www.nashbiotechs.com/nash-biotech-analysis/nash-introduc=on/what-is-known-about-nash.html

•  Non-alcoholicfaWyliverdisease(NAFLD)isoneofthecausesoffajyliver,occurringwhenfatisdeposited(steatosis)intheliverduetocausesotherthanexcessivealcoholuse.

•  Non-alcoholicsteatohepa99s(NASH)isthemostextremeformofNAFLD,andisregardedasamajorcauseofcirrhosisoftheliverofunknowncause

•  Causeiss=llunknownbutobesityandinsulinresistancelikelyplayastrongroleinpathology

•  NASHisgenerallyrecognizedastheliver’sexpressionofMetabolicSyndrome

WorldGastroenterologyOrganiza=on,2012Arslan.WorldJGastroenterol,2014

Title:Glucevia®limitsweightgainsandhyperglycemiainhigh-fatdiet-inducedobesemicePopula9on:C57BL/6Jmalemice(5weeksofage)Dura9on:16weeksDesign:•  HighFatDiet[60%fat](n=20)•  HFD+0.5%Glucevia®(n=10)•  LowFatDiet[60%fat](n=20)Outcomes:•  Fas=ngbloodglucose•  Fajylivers

Model:Highfatdietmice

-50%

-33%

Result:Significantlylowersthedevelopmentofhyperglycemiaazeradministra=onofahighfatdietby33%(p<0.001)

Result:Significantlyreducesfajyliverby50%

Ibarra et al. (2011) Phytomedicine,

Scien3ficsubstan3a3on–invivo

Title:Ac=onofanextractfromtheseedsofGlucevia®onmetabolicdisordersinhypertensiveandobeseanimalmodelsPopula9on:Zuckerrats(8weeksold)Design:Administered,for5weeks,adietcontaining:•  Nega=vecontrol:Noaddi=ve(n=6)•  Posi=vecontrol:Me}ormin(n=6)•  Glucevia(100mg/kgbw/day)(n=6)Outcomes:•  Glucosewasfollowedduringthe5weeksstudyResults:•  Significantlyreducesfas=ngbloodglucoseby

16%(p<0.001)•  NosignificantdifferencebetweenGluceviaand

Me}ormin.(Me}orministhereferencedrugforbloodglucosemanagement)

Model:Obesemice

0 1 2 3 4 5

-50

-25

0

25

50

75

Control

FXE100Metformin

******

Weeks of treatment

ΔG

luco

se(m

g/dL

)

-16 %

Monto et al. (2014). Food&Function


Title:Preven=veEffectofaGlucevia®onHepa=cSteatosisinObeseType2Diabe=cMicePopula9on:BKS(db/db)femalemice(5weeksofage)Design:7monthsadministra=onofControldiet(n=10)DietwithGlucevia(0,7g/kgofdiet)(n=10)Outcomes:Metabolicbloodparameters(glucose,insulin,cholesterol,triglycerides)HistologicalanalysesofliverNAFLDbloodparameters

Results•  Significantreduc=oninInsulin(p<0.05)•  SignificantimprovementinInsulin

resistance(p<0.05)•  Significantimprovementsinfajyliver

Model:Diabe3cmice

0

10

20

30

Control Glucevia™

Reduc9onoffatintheliver(in%)

-54%

-54%

Stained sections of livers from diabetic mice administered control or Glucevia® •  Micrographs of H&E (a vs. b) •  Oil red O (c vs. d)

Glucevia® Control

Gomez-Garcia et al. Journal of Diabetes & Metabolism, 2015


Title:AcuteeffectsofGlucevia®onpostprandialglycemiaandinsulinsecre=ononhealthyvolunteersPopula9on:16healthypeople(11male,5female;20-55y,BMI:26±2.2kg/m2).Design:Doubleblind,randomized,crossover(1weekwashoutperiod),acute,placebocontrolledclinicaltrial.Dose:1,000mgofGlucevia®oraPlacebo(Wheatbran),50gglucoseforOGTTOutcomes:Bloodglucose(0,15,30,45,60,90,120min)Results:Immediateandsignificantreduc=oninbloodglucoseAUCof9%(p>0.05)

AcuteHumanClinicalStudy

Visen et al., (2009) J. Ethnopharmacol., 126:226-232

020406080100

0 20 40 60 80 100 120B

lood

glu

cose

(mg/

dL)

Time (min)

Placeb

01000200030004000500060007000

Placebo Glucevia

Glu

cose

AU

C

(mg.

min

/dL)

- 9 % p<0.05

Scien3ficsubstan3a3on–clinical

Title:Glucevia®benefitsglucosehomeostasisandadiposityrelatedmarkersinelderlyoverweight/obesesubjects:Alongitudinal,randomized,crossover,double-blind,placebo-controllednutri=onalinterven=onstudy.Popula9on:17healthyvolunteers(50-80y,BMI:>25kg/m2).Design:Doubleblind,randomized,cross-over(21daysforeacharm),placebocontrolledinterven=onstudywithoneweekwash-outbetweenarms.Interven9ons:•  Recommenda=onforahealthydiet•  1,000mgofGlucevia®orplaceboOutcomes:•  OGTTbeforeandazereacharm•  MarkersofglycemiaResults:•  Significantreduc=oninbloodglucose(AUC)of28%inGlucevia

groupvs.Non-significantreduc=onof8%inplacebogroup.

ChronicHumanClinicalStudy

Zulet et al. (2014) Phytomedicine 21: 1162–1169

020406080100

0 20 40 60 80 100 120

Blo

od g

luco

se (m

g/dL

)

Time (min)

Pre-Glucevia

Effectof3-weekGlucevia®administra=ononbloodglucoselevels

Scien3ficsubstan3a3on–clinical

0

50

100

150

PriortoGluceviaAzerGluceviaPriortoplaceboAzerplacebo

2h b

lood

glu

cose

(mg/

dL)

-14.0 % p<0.05 -1.6 % n.s.

Results:Significant(p<0.05)reduc=onin2hbloodglucoselevel(-14%)observedRelevance:AccordingtotheWorldHealthOrganiza=onthe2hbloodglucosevalueisregardedasanindicatorofimpairedglucosetoleranceanddiabetes(>140mg/dL)

-20.00

-10.00

0.00

10.00

20.00

Glucevia Placebo

Cha

nge

in fr

ucto

sam

ine

(µM

)

p<0.05

Results:SignificantdifferenceinthechangeinfructosaminebetweengroupsRelevance:AccordingtoEFSA,Fructosamineisrelevantmarkerforglucosecontrolandthemostwidelyusedalterna=vetoHbA1c

Zulet et al. (2014) Phytomedicine 21: 1162–1169

Scien3ficsubstan3a3on–clinicalChronicHumanClinicalStudy-con3nued

Title:TargetedanduntargetedmetabolomicstoexplorethebioavailabilityofthesecoiridoidsfromGlucevia®inhumanhealthyvolunteers:apreliminarystudy

Popula9on:10healthyvolunteers(23.5y,BMI<30kg/m²).Design:open-labelledacutesingledosebioavailabilitystudywithatargetedanduntargetedmetabolomicsmethodologyOutcomes:•  Plasmametabolitesanalysisbeforeand1,2,4,8and24hazer

1000mgofGlucevia®intake•  Urinemetabolitesanalysisbeforeand1,2,4,8and24hazer

1000mgofGlucevia®intakeResults:Noparentcompounds(nuzhenideandGL3)foundinurineorplasmaSomepredictedmetabolitesdetectedatlowintensityDetec=onofpoten=alphenolicconjugatesandsulfatesderiva=vesofsecoiridoidsfromphaseIand/ormicrobialenzymesConclusion:TheeffectsofGluceviaseemnottobelinkedtoadirecteffectsofitsparentcompoundsbuttoandirectorindirecteffectoftheirmetabolites(humanorgutmicrobiota-derived).

Garcia-Villalba (2015) Molecules 20: 22202–22219

Wheredoesefficacycomefrom?

FajyLiver&MicrobiomeModula=onWorkingTitle:Glucevia®,aFraxinusangus3foliaVahlextract,isabletomodifythegutmicrobiotacomposi=onandthoseeffectsarecorrelatedwithsteatosisseverityinobeseanddiabe=cmice.Popula9on:MiceDesign:Administered,for12weeks,adietcontaining60%energyfromfatwithorwithoutGlucevia®(200mg/kgbw)Outcomes:Liverfatcontent,metagenomicsstudyonthefecalsamples

Unpublished

0

10

20

30

40

50

60

Control F.angus=folia

%offatcon

tentintoth

eliver

TheWorldGastroenterologyOrganiza=onhistologicalscoringsystemforsteatosis(Grade0:<5%,Grade1:5-33%,Grade2:34-66%,Grade3:>67%):Results:Control:35.2%-Grade2Glucevia®22.8%-Grade1(-35%vs.control)p=0.004

-35%,p=0.004

Control F.angus3folia

Glucevia protected against liver steatosis induced by 12 week high fat diet consumption in mice

HFD60_T3

HFD60+F.angust_T3HFD60_T3HFD60+F.angust_T3

Glucevia induced some modifications of the gut microbiota composition in mice fed a HFD during 12 weeks

FajyLiver&MicrobiomeModula=on

Unpublished

%OilRedLiverStain

%OilRedLiverStain

Rela9v

eab

unda

nce%

Rela9v

eab

unda

nce%

%OilRedLiverStain

%OilRedLiverStain

Rela9v

eab

unda

nce

%

Rela9v

eab

unda

nce

% %OilRedLiverStain

Rela9v

eab

unda

nce

%

The gut microbiota modifications are significantly correlated (positively or negatively depending on the bacterial groups) to the liver steatosis severity

FajyLiver&MicrobiomeModula=on

p=0.04

p=0.04

p=0.04

p=0.03

p=0.12

Unpublished

LongitudinalclinicalstudyinpreparaIonPopula9on:SubjectssufferingfromsteatosisandNASH(fibrosisscore<2),n=50Dura9on:6monthsMainclinicalendpoints:Liverfatcontent,gutandbloodmicrobiotametagenomic(shotgun)Objec9ves:•  Establishaproofofconceptofefficacyfor

improvementofNAFLDinhumans•  DemonstratethatGluceviaisableto

modifythegutmicrobiomeinhumans•  Demonstratethecorrela=onbetween

steatosisseverityandthemodifica=onofgutmicrobiomeinhumans

Con3nuedresearchprogram

Confirma=oninhumantobedone

Strategy for demonstrating the causative role of the gut microbiota in chronic diseases.

Zao.NatRevMicrob.2013

Howcanwereversedysbiosis?

Probio=cs are “livemicro-organisms which, whenadministered in adequate amounts,conferahealthbenefitonthehost“

(Defini=onFAO/WHO2012)

Prebio=csare“selec=velyfermentedingredientsthatpromotetheselec=ves=mula=onofgrowthand/orac=vi=esofoneoralimitednumberofmicrobialgenus(era)/speciesinthegutmicrobiotathatconfer(s)healthbenefitstothehost”(Defini=onfromGibson&Roberfroidetal,2010)

Symbio=cs

REBIOSIS:Establishingamicrobial

communitybacktoahealthystatePostbio=cs are “non-

viable bacterial products ormetabol ic byproducts fromprobio=c microorganisms thathavebiologicac=vityinthehost”(Defini=onPatel&Dening,2013)

Botanicals!Revisited & enlarged definition of prebiotics Bindels et al, Nat. Rev. Gastroenterol. Hepatol, 2015

Not an isolated case…

Therosemaryextractexample

Thehopextractexample

Acknowledgments

Leila Falcao

Melissa Feuillatre

R&D team

Elodie Riant

Aurélie Waget

Rémy Burcelin

Pierre Gourdy

Inserm UMR 1048/I2MC

Diabetology department ,

CHU de Toulouse Rocío García-Villalba

Pilar Zafrilla

María-Teresa García-Conesa

Francisco A. Tomás-Barberán

Thank you for your attention!

Visit us at www.naturex.com

Documents

Demystifying Microbiome Research: New Opportunities for ... · The human microbiota The term microbiota refers to the microbial populaon present within the human body, including bacteria,