MICROBIOTAGutmicrobiotautilizeimmunoglobulinAformucosalcolonizationG.P.Donaldson,1*M.S.Ladinsky,1K.B.Yu,1J.G.Sanders,2,3B.B.Yoo,1W.-C.Chou,4M.E.Conner,5A.M.Earl,4R.Knight,2,3P.J.Bjorkman,1S.K.Mazmanian1*Theimmunesystemrespondsvigorouslytomicrobialinfectionwhilepermittinglifelongcolonizationbythemicrobiome.Mechanismsthatfacilitatetheestablishmentandstabilityofthegutmicrobiotaremainpoorlydescribed.WefoundthataregulatorysystemintheprominenthumancommensalBacteroidesfragilismodulatesitssurfacearchitecturetoinvitebindingofimmunoglobulinA(IgA)inmice.Specificimmunerecognitionfacilitatedbacterialadherencetoculturedintestinalepithelialcellsandintimateassociationwiththegutmucosalsurfaceinvivo.TheIgAresponsewasrequiredforB.fragilis(andothercommensalspecies)tooccupyadefinedmucosalnichethatmediatesstablecolonizationofthegutthroughexclusionofexogenouscompetitors.Therefore,inadditiontoitsroleinpathogenclearance,weproposethatIgAresponsescanbeco-optedbythemicrobiometoengenderrobusthost-microbialsymbiosis.Atbirth,ecologicalandevolutionarypro-cessescommencetoassembleacomplexmicrobialconsortiumintheanimalgut.Communitycompositionoftheadulthu-mangutmicrobiomeisremarkablystableduringhealth,despiteday-to-dayvariabilityindietanddiverseenvironmentalexposures.In-stability,ordysbiosis,maybeinvolvedintheetiologyofavarietyofimmune,metabolic,andneurologicdiseases(1,2).Longitudinalsequenc-ingstudiesindicatethatamajorityofbacterialstrainspersistwithinanindividualforyears(3),andformostspeciesthereisasingle,persist-entlydominantstrain(4)(termed“single-strainstability”).Mucusandcomponentsoftheinnateandadaptiveimmunesystemsarethoughttoinfluencemicrobiomestability,independentlyofdiet.Forexample,immunoglobulinA(IgA),themainantibodyisotypesecretedinthegut,shapesthecompositionoftheintestinalmicro-biomeviacurrentlyunknownmechanisms(5–8).IgAdeficiencyinmiceincreasesinterindividualvariabilityinthemicrobiome(9)anddecreasesdiversity(10,11).ThedirecteffectsofIgAonbacteriahavelargelybeenstudiedinthecontextof...
