RegulationofinflammationbymicrobiotainteractionswiththehostJMagarianBlander1,2,3,RandySLongman1,2,IliyanDIliev1,2,GregoryFSonnenberg1,2,3,andDavidArtis1,2,31JillRobertsInstituteforResearchinInflammatoryBowelDisease,JoanandSanfordI.WeillDepartmentofMedicine,WeillCornellMedicine,CornellUniversity,NewYork,NewYork,USA2DepartmentofMicrobiologyandImmunology,WeillCornellMedicine,CornellUniversity,NewYork,NewYork,USA3SandraandEdwardMeyerCancerCenter,WeillCornellMedicine,CornellUniversity,NewYork,NewYork,USAAbstractThestudyoftheintestinalmicrobiotahasbeguntoshiftfromcatalogingindividualmembersofthecommensalcommunitytounderstandingtheircontributionstothephysiologyofthehostorganisminhealthanddisease.Here,wereviewtheeffectsofthemicrobiomeoninnateandadaptiveimmunologicalplayersfromepithelialcellsandantigen-presentingcellstoinnatelymphoidcellsandregulatoryTcells.Wediscussrecentstudiesthathaveidentifieddiversemicrobiota-derivedbioactivemoleculesandtheireffectsoninflammationwithintheintestineanddistallyatsitesasanatomicallyremoteasthebrain.Finally,wehighlightnewinsightsintohowthemicrobiomeinfluencesthehostresponsetoinfection,vaccinationandcancer,aswellassusceptibilitytoautoimmuneandneurodegenerativedisorders.Anastoundingnumberanddiversityofmicroorganismscoexistwithmammalianorganisms1.Recentyearshaveseenanincreaseinunderstandingofthecomplexityandsophisticationofthehost–microbiotarelationshipanditseffectsonhumanhealth2–4.Severaltechnologicaladvanceshavebolsteredthestudyofmammalianmicrobiomes.Sequencingof16S-rRNA-encodinggeneshasidentifiedtheconstituentbacterialspeciesofthehumanintestinalmicrobiotaasbelongingpredominantlytotheBacteroidetesandFirmicutesphyla.Deepsequencingoftheinternal-transcribed-spacerregionsITS1andITS2ofthefungalribosomalDNAandimproveddownstreamanalyses5,6haveunveiledthepresenceofrichfungalcommunities,dubbedthemycobiome,withinthemammalianintestinaltract7.SequencingoftotalDNA,themetagenome,fromfecalspecimenshasenabledsystematicstudiesontheviromeandhasyieldedvalu...
