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1、ARTicLEdoi:10.1038/nature23874CommensalbacteriamakeGPCRligandsthatmimichumansignallingmoleculesLouisJ.cohen1,2,DariaEsterhazy3,seong-HwanKim1,christopheLemetre1,RhiannonR.Aguilar1,EmmaA.Gordon1,AmandaJ.pickard4,JustinR.cross4,Anab.Emiliano5,sunm.Han1
2、,Johnchu1,XavierVila-Farres1,JeremyKaplitt1,AnetaRogoz3,paulaY.calle1,craigHunter6,J.Kipchirchirbitok1&seanF.brady1Commensalbacteriaarebelievedtohaveimportantrolesinhumanhealth.Themechanismsbywhichtheyaffectmammalianphysiologyremainpoorlyunderstood,b
3、utbacterialmetabolitesarelikelytobekeycomponentsofhostinteractions.HereweusebioinformaticsandsyntheticbiologytominethehumanmicrobiotaforN-acylamidesthatinteractwithG-protein-coupledreceptors(GPCRs).WefoundthatN-acylamidesynthasegenesareenrichedingast
4、rointestinalbacteriaandthelipidsthattheyencodeinteractwithGPCRsthatregulategastrointestinaltractphysiology.Mouseandcell-basedmodelsdemonstratethatcommensalGPR119agonistsregulatemetabolichormonesandglucosehomeostasisasefficientlyashumanligands,althoug
5、hfuturestudiesareneededtodefinetheirpotentialphysiologicalroleinhumans.Ourresultssuggestthatchemicalmimicryofeukaryoticsignallingmoleculesmaybecommonamongcommensalbacteriaandthatmanipulationofmicrobiotagenesencodingmetabolitesthatelicithostcellularre
6、sponsesrepresentsapossiblesmall-moleculetherapeuticmodality(microbiome-biosyntheticgenetherapy).Althoughthehumanmicrobiomeisbelievedtohaveanimportantsmallmoleculesandtheirassociatedmicrobialbiosyntheticgeneshaveroleinhumanphysiology,themechanismsbywh
7、ichbacteriaaffectthepotentialtoregulatehumanphysiology.mammalianphysiologyremainpoorlydefined1.Bacteriarelyheavilyonsmallmoleculestointeractwiththeirenvironment2.AlthoughitisIsolationofcommensalN-acylamideslikelythatthehumanmicrobiotasimilarlyrelieso
8、nsmallmoleculestoToidentifyN-acylsynthase(NAS)geneswithinhumanmicrobialinteractwithitshumanhost,theidentityandfunctionsofmicrobiota-genomes,theHumanMicrobiomeProject(HMP)sequencedataencodedeffectormoleculesremainmostlyunknown.Thestudyofwassearchedwit
