UnderstandingtheHolobiont:HowmicrobialmetabolitesaffecthumanhealthandshapetheimmunesystemThomasSiegmundPostlerandSankarGhosh*DepartmentofMicrobiology&Immunology,CollegeofPhysicians&Surgeons,ColumbiaUniversity,NewYork,NY10032,USASUMMARYThehumangastrointestinaltractispopulatedbyadiverse,highlymutualisticmicrobialflora,whichisknownasthemicrobiome.Disruptionstothemicrobiomehavebeenshowntobeassociatedwithseverepathologiesofthehostincludingmetabolicdisease,cancerandinflammatoryboweldisease.Moodandbehaviorarealsosusceptibletoalterationsinthegutmicrobiota.Aparticularlystrikingexampleofthesymbioticeffectsofthemicrobiomeistheimmunesystem,whosecellsdependcriticallyonadiversearrayofmicrobialmetabolitesfornormaldevelopmentandbehavior.Thisincludesmetabolitesthatareproducedbybacteriafromdietarycomponents;metabolitesthatareproducedbythehostandbiochemicallymodifiedbygutbacteria;andmetabolitesthataresynthesizeddenovobygutmicrobes.Inthisreview,wehighlighttheroleoftheintestinalmicrobiomeinhumanmetabolicandinflammatorydiseasesandfocusinparticularonthemolecularmechanismsthatgovernthegut-immuneaxis.KeywordsMicrobiome;commensals;atherosclerosis;metabolicsyndrome;inflammatoryboweldisease;short-chainfattyacids;indole;polysaccharideA;polyamine;obesityABriefHistoryofMicrobiomeResearchScientificinvestigationofthenon-pathogenicbacteriathatpopulatethemammaliangastrointestinaltract,collectivelyreferredtoasthegutmicrobiome1,hasalonghistory.Welloveracenturyago,studiesdemonstratedthatdietarychangescanalterthetypeofmetabolitesproducedbybacterialivinginthehealthyintestine(Hirschler,1886),andthat*Correspondingauthor:SankarGhosh,Ph.D.,DepartmentofMicrobiology&Immunology,ColumbiaUniversity,CollegeofPhysicians&Surgeons,HHSC1210,701West168thStreet,NewYork,NY10032,USA,Phone:+1(212)304-5257,sg2715@cumc.columbia.edu.ORCIDIDforTSP:0000-0002-3558-9084Publisher'sDisclaimer:ThisisaPDFfileofanuneditedmanuscriptthathasbeenacceptedforpublication.Asaservicetoourcustomersweareprovidingthisearlyversionofthemanuscript...
