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InfectionandGutMicrobiota

Yao-JongYang 

1,2 

andBor-ShyangSheu 

2,3,*

1

DepartmentsofPediatrics,NationalChengKungUniversityHospital,MedicalCollege,NationalChengKungUniversity,#138ShengLiRoad,Tainan70428,Taiwan

2

InstituteofClinicalMedicine,MedicalCollege,NationalChengKungUniversity,Tainan70428,Taiwan

3

DepartmentofInternalMedicine,NationalChengKungUniversityHospital,CollegeofMedicine,NationalChengKungUniversity,#138ShengLiRoad,Tainan70428,Taiwan

*

Correspondence:

Tel.:

+886-6-235-3535（ext.5368）

AcademicEditor:

CarlGordonJohnston

Received:

6August2015/Accepted:

5February2016/Published:

16February2016

Abstract

:

Asabarrier,gutcommensalmicrobiotacanprotectagainstpotentialpathogenicmicrobesinthegastrointestinaltract.Crosstalkbetweengutmicrobesandimmunecellspromoteshumanintestinalhomeostasis.Dysbiosisofgutmicrobiotahasbeenimplicatedinthedevelopmentofmanyhumanmetabolicdisorderslikeobesity,hepaticsteatohepatitis,andinsulinresistanceintype2diabetes（T2D）.Certainmicrobes,suchasbutyrate-producingbacteria,arelowerinT2Dpatients.Thetransferofintestinalmicrobiotafromleandonorsincreasesinsulinsensitivityinindividualswithmetabolicsyndrome,buttheexactpathogenesisremainsunclear. 

H.pylori 

inthehumanstomachcausechronicgastritis,pepticulcers,andgastriccancers. 

infectionalsoinducesinsulinresistanceandhasbeendefinedasapredisposingfactortoT2Ddevelopment.GastricandfecalmicrobiotamayhavebeenchangedinH.pylori-infectedpersonsandmicetopromotegastricinflammationandspecificdiseases.However,theinteractionof 

andgutmicrobiotainregulatinghostmetabolismalsoremainsunknown.Furtherstudiesaimtoidentifythe 

H.pylori-microbiota-hostmetabolismaxisandtotestif 

eradicationormodificationofgutmicrobiotacanimprovethecontrolofhumanmetabolicdisorders.

Keywords:

H.pylori;

microbiota;

metabolicinteraction;

insulinresistant;

diabetes

1.Introduction

Thehumangut,includingthestomachandintestine,isinhabitedbyavastnumberofmicroorganismsthathostmicrobiota[1].Gutmicrobiotastartsafterbirththroughcontactwiththemother’svaginal,skin,andfecalmicroorganisms[2,3]anditsecologyisinfluencedbythedeliverytype,maternaldiet,gestationalage,andantibioticexposure[4,5,6].Usingnewmetagenomicstechniques,researchershavedemonstratedthatgutmicrobiotaregulatethehostimmunehomeostasisandarerelatedtomanyhumanmetabolicdisorders[7].Inananimalstudy,thegutmicrobiomeincreasedthecapacityofobesemicetoharvestenergyfromtheirdiet[8].Moreover,thetransmissionofmicrobiotafromobesemicetogerm-freemiceledtoincreasedtotalbodyfat[8].Thus,theintegrityandbalanceofgutmicrobiotaplayamajorroleinthemetabolicinteractionbetweenthehostandthemicrobialcommunity.

canpersistentlycolonizethegastricepitheliumbyinteractingwithbacterialadhesionmoleculesandgastricreceptors[9,10].Themetabolicconsequencesof 

infectionhavebeenreportedtochangethemicrobial-originfattyacidandlipidprofilesinhostblood[11].InananimalstudythatusedNMR-basedmetabolicanalysis, 

H.pyloriinfectionwasshowntodisturbthecarbohydrateandaminoacidmetabolismofthehost[12].Inaddition,metabolicchangesareassociatedwiththediversityofgutmicrobiota.Takentogether,thesestudiesindicatethatthehomeostasisandsystemicmetabolismbetweengutmicrobiotaandthehostmaybealteredby 

H.pylori.However,theexactmechanismremainsunclear.Thisreviewarticlefocusedonthemetabolicinteractionbetweengutmicrobiotaand 

H.pylori,aswellastherelatedconsequencesofsuchinteractiononthehost’shealth.

2.CrosstalkbetweenMicrobiotaandIntestines

Gutmicrobialcommunitiesareknowntobeinheritedfromthemother[2,3].Severalstudieshaveshownthathumanhealthissusceptibletointeractionsbetweengutmicrobiotadiversityorcompositionandintestinalcells[1,3].Mucosalandimmunehomeostasiscanbeestablishedbyabalancedinteractionbetweenmicrobialsignalsandhostimmunecells[2,13].Inmicestudies,Ivanov 

etal.demonstratedthatasinglesegmentedfilamentousbacteriumcaninduceeffectorTcelldifferentiationinthelaminapropria[14].OtherreportsshowthatcertaincommensalbacteriamodulateintestinalinflammatoryresponsesbyinducingregulatoryT（Treg）cellsandthedownstreamproductionoftransforminggrowthfactor-β（TGF-β）andinterleukin-10（IL-10）[15,16].Mortha 

etal. 

reportedthatintestinalmacrophagescouldsensemicrobialsignalstoinducetheRORγt+ 

innatelymphoidcells（ILCs）toproducecolony-stimulatingfactor2（CSF2）,therebypromotingintestinalhomeostasis[13].Allofthesesuggestthatautoimmunediseasescausedbytheinnate-adaptiveimmuneactivationarelikelytobeaffectedbythemicrobialenvironment[17].

3.MetabolicRolesofGutMicrobiota

Crosstalkandsignalingbetweenthehostandmicrobiotaoccuratboththecellularandmetaboliclevels.Ktsoyan 

etal.showedthatsignificantconcentrationsofmicrobiallongchainfattyacids（LCFAs）werepresentinhumanbloodandcorrespondedtospecificmicrobialcompounds[11].Furthermore,theprofileoftheseLCFAsisdistinguishedbetweenhealthyandpathologicstates.Commensalmicrobiotacanbreakdownindigestiblepolysaccharidesinthediet,therebyservingas70%oftheenergysource.Usinggenomicanalysis,studiesrevealedthathumancolonicmicrobeslikeBacteroides 

and 

Bifidobacterium 

possessedabundantpolysaccharidesandstarchbreakdowngenes[18,19,20].

Theotherimportantenergysourceofbacterialcolonizersoftheepithelium,especiallybutyratefermentingbacteria,isshortchainfattyacids（SCFA）[21].Microbe-producingbutyratemayserveasnutrientsforcellgrowthbutalsoasaugmentationofthebarrierfunctiontopreventcarcinogenesisofthecolonicepithelium[22,23].Usingthe16SrRNAsequencingmethod,Pryde 

demonstratedthatthemostcommonbutyrate-producingbacteriawere 

Clostridium 

spp.,particularinclustersXIVaandIVinthehumanfeces[21].DecreasedproductionofSCFAscanalsobecorrelatedtocolonicinflammationandclinicaldiseases.Kelly 

revealedthatmicrobe-derivedSCFAs,particularlybutyrate,stimulatedepithelialmetabolismanddecreasedintracellularO2,resultinginthestabilizationofthetranscriptionfactorhypoxia-induciblefactor-1（HIF-1）andepithelialbarrierfunction[22].Inaratmodelofcoloncancer,Mclntyre 

etal.reportedthatratsfedahighbutyrate-producingfiberdiet（wheatbran）hadsignificantlyfewertumorsandlesstumormassthanthosegivenlowbutyrate-productionfiberdiet[23].Theseresultsimplythatgutmicrobiotainfluenceslocalandsystemicmetabolites,andcloselydeterminatesimmunityandotherprotectivemechanismsinhumans（Figure1）.

Figure1. 

Themetabolicandimmunologicrolesofgutmicrobiotaand 

H.pyloriinfectiononhumanmetabolicdisorders.IPS,indigestiblepolysaccharides;

SCFA,short-chainfattyacid;

LDL,low-densitylipoprotein;

HDL,high-densitylipoprotein.

4.GutDysbiosisandHumanMetabolicDisorders

Analteredbalancebetweengutmicrobiotaandthehostcontributestoaspectrumofimmune,inflammatory,andmetabolicdisorders.Ametagenome-wideassociationstudyusingdeepshotgunsequencingofthegutmicrobialDNAdemonstratedthattype2diabetes（T2D）inChinesepatientshadmoderatedegreesofgutmicrobiotadysbiosis,particularlydecreasedbutyrate-producingbacteria[24].Basedonthecloseassociationbetweenmicrobiotaanddiabetes,Vrieze 

etal.transferredintestinalmicrobiotafromleandonorstorecipientmaleswithmetabolicsyndrome.Sixweekslater,theinsulinsensitivityoftherecipientsincreasedalongwithlevelsofbutyrate-producingintestinalmicrobiota[25].

Wen 

usedatype1diabetes（T1D）non-obesediabetic（NOD）micemodeltosuggestthatsignalingthroughtheMyD88adaptorwascriticalforT1Ddevelopment.Thiseffectdependedoncommensalmicrobesbecausegerm-freeMyD88-negativeNODmicedevelopedrobustdiabetes[26].Moreover,thetransplantationofmicrobiotafromspecificpathogen-freeMyD88-negativeNODdonorstogerm-freeNODrecipientsattenuatedtheT1D.Takentogether,alterationsinintestinalmicrobiotaareassociatedwithinsulinresistanceanddiabetes.Therestorationof“healthymicrobiota”（microbiotainhealthycondition）maybeapromisingtherapeuticstrategyforcontrollingmetabolicsyndrome.

5. 

InfectionandMetabolicDiseases

IdentifiedbyMarshallandWarrenin1984, 

cancausechronicgastritisandpepticulcerdisease[27,28].TheWorldHealthOrganization（WHO）hascategorized 

asagroupIcarcinogen,emphasizingitsassociationwithgastriccancer[29]. 

havealsobeenassociatedwithseveralextra-gastricdiseaseslikeirondeficiencyanemia,idiopathicthrombocytopenicpurpura,andchildhoodgrowth[30,31,32].Althoughtheexactrelationshipbetween 

anddiseasesisstillbeingdebated,bacterialeradicationresultsinlong-termbenefits[33,34].Recently,studiesdemonstratedthat 

infectionwasalsorelatedtolipidandglucosemetabolism[35,36].Alarge-scalecross-sectionalstudyrevealedthatmaleswhowere 

H.pylori-seropositiveexhibitedsignificantlyhigherlow-densitylipoprotein（LDL）cholesterollevelsandsignificantlylowerhigh-densitylipoprotein（HDL）cholesterollevelsthan 

H.pylori-seronegativesubjects[37].Jia 

suggestedtha