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Interplay between diet and gut microbiome, and

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1Li J,et al.Gut2021;0:1–10.doi:10.1136/gutjnl-2020-322473GutmicrobiotaOriginalresearchInterplaybetweendietandgutmicrobiome,andcirculatingconcentrationsoftrimethylamineN-oxide:findingsfromalongitudinalcohortofUS menJunLi,1,2YanpingLi,1KerryLIvey,1,3DongDWang,1,4JeremyEWilkinson,5AdrianFranke,6KyuHaLee,1,2,5AndrewChan,7,8CurtisHuttenhower,5,8,9FrankBHu,1,2,4EricBRimm,1,2,4QiSun1,2,4Tocite:Li J,Li Y,Ivey KL,et al.GutEpubaheadofprint:[pleaseincludeDayMonthYear].doi:10.1136/gutjnl-2020-322473►Additionalsupplementalmaterialispublishedonlineonly.Toview,pleasevisitthejournalonline(http://dx.doi.org/10.1136/gutjnl-2020-322473).Fornumberedaffiliationsseeendofarticle.CorrespondencetoDrQiSun,DepartmentofNutrition,HarvardUniversityTHChanSchoolofPublicHealth,Boston,MA02115,USA;qisun@hsph.harvard.eduEBRandQScontributedequally.Received7July2020Revised15April2021Accepted18April2021©Author(s)(ortheiremployer(s))2021.Nocommercialre-use.Seerightsandpermissions.PublishedbyBMJ.ABSTRACTObjectivesGut-producedtrimethylamineN-oxide(TMAO)ispostulatedasapossiblelinkbetweenredmeatintakeandpoorcardiometabolichealth.WeinvestigatedwhethergutmicrobiomecouldmodifyassociationsofdietaryprecursorswithTMAOconcentrationsandcardiometabolicriskmarkersamongfree-livingindividuals.DesignWecollecteduptotwopairsoffaecalsamples(n=925)andtwobloodsamples(n=473),6monthsapart,from307healthymenintheMen’sLifestyleValidationStudy.Dietwasassessedrepeatedlyusingfood-frequencyquestionnairesanddietrecords.Weprofiledfaecalmetagenomeandmetatranscriptomeusingshotgunsequencingandidentifiedmicrobialtaxonomicandfunctionalfeatures.ResultsTMAOconcentrationswereassociatedwiththeoverallmicrobialcompositions(permutationalanalysisofvariance(PERMANOVA)testp=0.001).Multivariabletaxa-wideassociationanalysisidentified10bacterialspecieswhoseabundancewassignificantlyassociatedwithplasmaTMAOconcentrations(falsediscoveryrate<0.05).HigherhabitualintakeofredmeatandcholinewassignificantlyassociatedwithhigherTMAOconcentrationsamongparticipant

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