腸道菌群與代謝疾病課件

腸道菌群與代謝疾病1腸道菌群與代謝疾病1目錄腸道菌群與健康和疾病概述腸-腦軸腸-肝軸腸道菌群與代謝性疾?。悍逝帧⑻悄虿∧c道菌群與腸病腸道菌群與免疫腸道菌群與其它疾病革命帶來的挑戰(zhàn)和機遇2目錄2悄悄發(fā)生的革命INNASEKIROV,etal.,GutMicrobiotainHealthandDisease.PhysiolRev90:859–904,2010;3悄悄發(fā)生的革命INNASEKIROV,etal.,G一篇值得關(guān)注的綜述Naturereviews.Microbiology最新的影響因子為22.490(2013)4一篇值得關(guān)注的綜述Naturereviews.Micro人菌共生KristinaHarris,etal.,IstheGutMicrobiotaaNewFactorContributingtoObesityandItsMetabolicDisorders?JournalofObesity,Volume2012,p1-14.5人菌共生KristinaHarris,etal.,Is人腸道菌群種類和數(shù)量EAMONNM.M.QUIGLEYandRODRIGOQUERA,SmallIntestinalBacterialOvergrowth:RolesofAntibiotics,Prebiotics,andProbiotics.GASTROENTEROLOGY2006;130:S78–S906人腸道菌群種類和數(shù)量EAMONNM.M.QUIGLEY好細菌和壞細菌7好細菌和壞細菌7菌群是健康的核心NathalieM.Delzenne,etal.,Targetinggutmicrobiotainobesity:effectsofprebioticsandprobiotics.Nat.Rev.Endocrinol.7,639–646(2011).8菌群是健康的核心NathalieM.Delzenne,腸道菌群對人生理的影響9腸道菌群對人生理的影響9腸道菌群-代謝產(chǎn)物-功能JeremyK.Nicholsonetal.,Host-GutMicrobiotaMetabolic.Science336,1262-1267,2012.10腸道菌群-代謝產(chǎn)物-功能JeremyK.Nicholso影響腸道菌群的因素NathalieM.Delzenne&PatriceD.Cani,InteractionBetweenObesityandtheGutMicrobiota:RelevanceinNutrition.Annu.Rev.Nutr.2011.31:15–31.11影響腸道菌群的因素NathalieM.Delzenne影響腸道菌群的因素12影響腸道菌群的因素12腸-腦軸/腦-腸軸13腸-腦軸/腦-腸軸13GermFree(GF)MiceDisplayIncreasedMotorActivityandReducedAnxiety-LikeBehavior.resultssuggestthatthemicrobialcolonizationprocessinitiatessignalingmechanismsthataffectneuronalcircuitsinvolvedinmotorcontrolandanxietybehavior.14GermFree(GF)MiceDisplayIn腸-腦軸的概念A(yù)ugustoJ.Montiel-Castro,etal.,Themicrobiota–gut–rainaxis:neurobehavioralcorrelates,healthandsociality.FrontinIntegNeuro.Oct2013|Vol7|Article70|1-16.15腸-腦軸的概念A(yù)ugustoJ.Montiel-Cast腦-腸軸/腸-腦軸：迷走神經(jīng)SueGrenham,etal.,Brain–gut–microbecommunicationinhealthanddisease.FrontiersinPhysio.GastrointSciDec2011Vol2p1-15.16腦-腸軸/腸-腦軸：迷走神經(jīng)SueGrenham,eta腸腦軸/腦腸軸Q.AZIZ,etal.,Gutmicrobiotaandgastrointestinalhealth:currentconceptsandfuturedirections.NeurogastroenterolMotil(2013)25,4–15.17腸腦軸/腦腸軸Q.AZIZ,etal.,Gutmi菌群影響神經(jīng)功能EamonnM.M.Quigley.Dopatientswithfunctionalgastrointestinaldisordershaveanalteredgutflora?TherAdvGastroenterol(2009)2(Suppl1)S23–S30.18菌群影響神經(jīng)功能EamonnM.M.Quigley.D菌群紊亂致焦慮和抑郁JaneA.FosterandKaren-AnneMcVeyNeufeld,Gut–brainaxis:howthemicrobiomeinfluencesanxietyanddepression.TrendsinNeurosciences,May2013,Vol.36,No.5,P305-31219菌群紊亂致焦慮和抑郁JaneA.FosterandK精神活動影響腸道菌群JasonA.Hawrelak&StephenP.Myers,TheCausesofIntestinalDysbiosis:AReview.AlternMedRev2004;9(2):180-197.exposuretopsychologicalstressresultsinasignificantreductionintheproductionofmucinandadecreasedpresenceofacidicmucopolysaccharidesonthemucosalsurface.20精神活動影響腸道菌群JasonA.Hawrelak&應(yīng)激/壓力引起胃腸疾病P.C.KONTUREK,etal.,STRESSANDTHEGUT:PATHOPHYSIOLOGY,CLINICALCONSEQUENCES,DIAGNOSTICAPPROACHANDTREATMENTOPTIONS.JPHYSIO&PHARM2011,62,6,591-599.21應(yīng)激/壓力引起胃腸疾病P.C.KONTUREK,eta腦腸軸紊亂導(dǎo)致潰瘍P.C.KONTUREK,etal.,STRESSANDTHEGUT:PATHOPHYSIOLOGY,CLINICALCONSEQUENCES,DIAGNOSTICAPPROACHANDTREATMENTOPTIONS.JPHYSIO&PHARM2011,62,6,591-599.22腦腸軸紊亂導(dǎo)致潰瘍P.C.KONTUREK,etal.應(yīng)激導(dǎo)致IBDP.C.KONTUREK,etal.,STRESSANDTHEGUT:PATHOPHYSIOLOGY,CLINICALCONSEQUENCES,DIAGNOSTICAPPROACHANDTREATMENTOPTIONS.JPHYSIO&PHARM2011,62,6,591-599.23應(yīng)激導(dǎo)致IBDP.C.KONTUREK,etal.,應(yīng)激導(dǎo)致IBSP.C.KONTUREK,etal.,STRESSANDTHEGUT:PATHOPHYSIOLOGY,CLINICALCONSEQUENCES,DIAGNOSTICAPPROACHANDTREATMENTOPTIONS.JPHYSIO&PHARM2011,62,6,591-599.24應(yīng)激導(dǎo)致IBSP.C.KONTUREK,etal.,慢性疲勞與腸-腦軸25慢性疲勞與腸-腦軸252626腸道菌群和自閉癥GIbarrierdefectsandmicrobiotaalterationsinthematernalimmuneactivation(MIA)mousemodelthatisknowntodisplayfeaturesofASD.OraltreatmentofMIAoffspringwiththehumancommensalBacteroidesfragiliscorrectsgutpermeability,altersmicrobialcomposition,andamelioratesdefectsincommunicative,stereotypic,anxiety-likeandsensorimotorbehaviors.autism,andlikelyotherbehavioralconditions,arepotentiallydiseasesinvolvingthegutthatultimatelyimpacttheimmune,metabolic,andnervoussystems,andthatmicrobiome-mediatedtherapiesmaybeasafeandeffectivetreatmentfortheseneurodevelopmentaldisorders.thesefindingssupportagut-microbiome-brainconnectioninamousemodelofASDandidentifyapotentialprobiotictherapyforGIandparticularbehavioralsymptomsinhumanneurodevelopmentaldisorders.ElaineY.Hsiao,etal.,MicrobiotaModulateBehavioralandPhysiologicalAbnormalitiesAssociatedwithNeurodevelopmentalDisorders.Cell155,1451–1463,27腸道菌群和自閉癥GIbarrierdefectsand腸-腦軸和自閉癥CarolineG.M.deTheije,etal.,Pathwaysunderlyingthegut-to-brainconnectioninautismspectrumdisordersasfuturetargetsfordiseasemanagement.EuropeanJournalofPharmacology668(2011)S70–S8028腸-腦軸和自閉癥CarolineG.M.deTheij腸-肝軸EamonnM.M.Quigley,GutBacteriainHealthandDisease.Gastro&HepatVol9,9,2013,P560-569.1998年馬歇爾提出了“腸-肝軸”的概念對腸道和肝臟功能關(guān)系的認識提示新的治療理念,為腸道和肝臟疾病的治療探尋新的治療靶點。29腸-肝軸EamonnM.M.Quigley,Gut腸-肝軸之間的互動腸道菌群失調(diào)，大量G-桿菌繁殖,LPS產(chǎn)生顯著增多腸粘膜屏障功能受損

致病菌和LPS大量移位，經(jīng)門靜脈入肝，損害肝功能。肝功能異常KCs代謝和清除LPS降低，導(dǎo)致腸道功能異常GakuheiSon,etal.,ContributionofGutBacteriatoLiverPathobiology.GastroeResandPrac,Vol2010,ArticleID453563,13pages.30腸-肝軸之間的互動肝功能異常KCs代謝和清除LPS降低，導(dǎo)致腸肝對話31腸肝對話31腸道菌群致非酒精性脂肪肝ValentinaTremaroli&FredrikB?ckhed,Functionalinteractionsbetweenthegutmicrobiotaandhostmetabolism.NATURE|VOL489|13SEPTEMBER201232腸道菌群致非酒精性脂肪肝ValentinaTremarol腸道菌群導(dǎo)致脂肪肝CarmineFinelliandGiovanniTarantino,NONALCOHOLICFATTYLIVERDISEASE,DIETANDGUTMICROBIOTA.

EXCLIJournal2014;13:461-49033腸道菌群導(dǎo)致脂肪肝CarmineFinelliandG肝臟疾病和SIBO34肝臟疾病和SIBO34腸道菌群與代謝性疾病35腸道菌群與代謝性疾病35腸道菌群增加能量儲存NathalieM.Delzenne&PatriceD.Cani,InteractionBetweenObesityandtheGutMicrobiota:RelevanceinNutrition.Annu.Rev.Nutr.2011.31:15–31.36腸道菌群增加能量儲存NathalieM.Delzenne腸道菌群導(dǎo)致能量聚集PatriceDCaniandNathalieMDelzenne,Interplaybetweenobesityandassociatedmetabolicdisorders:newinsightsintothegutmicrobiota.CurrentOpinioninPharmacology2009,9:737–743.37腸道菌群導(dǎo)致能量聚集PatriceDCaniandN腸道菌群引發(fā)多種代謝疾病38腸道菌群引發(fā)多種代謝疾病3839394040腸道菌群和肥胖41腸道菌群和肥胖41腸道菌群和肥胖是一個新的熱門話題42腸道菌群和肥胖是一個新的熱門話題42肥胖的定義肥胖病一般被定義作為有BMI30以上。體重將近900磅(約400公斤)的里基(RickyNaputi)現(xiàn)年39歲，是世界最重的男子之一。因為體型過于笨重而難以移動，他已經(jīng)在坐落于太平洋關(guān)島的家中躺了五年之久。43肥胖的定義肥胖病一般被定義作為有BMI30以上。體重將肥胖和正常人AmandineEverard&PatriceD.Cani,Diabetes,obesityandgutmicrobiota.BestPractice&ResearchClinicalGastroenterology27(2013)73–83.44肥胖和正常人AmandineEverard&Patri史氏甲烷短桿菌和肥胖為了確定腸道菌群的改變和驗證人體腸道中的乳桿菌或雙歧桿菌是否與肥胖或消瘦相關(guān)，我們采用定量PCR和乳桿菌選擇性培養(yǎng)基分析了68位肥胖志愿者和47位對照的糞便菌群中硬壁菌、擬桿菌、乳酸乳球菌、動物雙歧桿菌和若干乳桿菌種的數(shù)量。結(jié)果：定量PCR試驗中，動物雙歧桿菌(OR=0.63;95%CI0.39-1.01;P=0.056)和史氏甲烷短桿菌(OR=0.76;95%CI0.59-0.97;P=0.03)與正常體重相關(guān)，而羅伊氏乳桿菌(OR=1.79;95%CI1.03-3.10;P=0.04)與肥胖相關(guān)。MillionM,etal.,Obesity-associatedgutmicrobiotaisenrichedinLactobacillusreuterianddepletedinBifidobacteriumanimalisandMethanobrevibactersmithii.IntJObes(Lond).2011Aug9.45史氏甲烷短桿菌和肥胖為了確定腸道菌群的改變和驗證人體腸道中的產(chǎn)甲烷肥胖的人有較高的身體質(zhì)量指數(shù)58人，BMI顯著較高的甲烷陽性者（45.2±2.3公斤/米2）比甲烷陰性（38.5±0.8公斤/米2，P=0.001）。甲烷陽性者也有更大程度的便秘與甲烷相比，陰性者（21.3±6.4比9.5±2.4，P?=.043）。多元回歸分析說明了BMI甲烷之間有顯著的關(guān)系。結(jié)論：這是人類第一次有研究表明，較高濃度的甲烷檢測呼氣測試是預(yù)測顯著更大的肥胖超重者。B.Basseri等，肝臟病雜志胃腸病學(xué)雜志，2012年1月8（1）：22-28美國Cedars-Sinai醫(yī)學(xué)中心46產(chǎn)甲烷肥胖的人有較高的身體質(zhì)量指數(shù)58人，BMI顯著較高的甲腸道菌群致肥胖原因ValentinaTremaroli&FredrikB?ckhed,Functionalinteractionsbetweenthegutmicrobiotaandhostmetabolism.NATURE|VOL489|13SEPTEMBER201247腸道菌群致肥胖原因ValentinaTremaroli&腸道菌群致肥胖原理JOHNK.DIBAISE,etal.,GutMicrobiotaandItsPossibleRelationshipWithObesity.MayoClinProc.2008;83(4):460-469.48腸道菌群致肥胖原理JOHNK.DIBAISE,eta不同胖瘦人群腸道菌群數(shù)量FabriceArmougom,etal.,MonitoringBacterialCommunityofHumanGutMicrobiotaRevealsanIncreaseinLactobacillusinObesePatientsandMethanogensinAnorexicPatients.PLoSONE4(9):e7125.49不同胖瘦人群腸道菌群數(shù)量FabriceArmougom,腸道菌群和糖尿病50腸道菌群和糖尿病50腸道菌群和I型糖尿病51腸道菌群和I型糖尿病51腸道菌群和I型糖尿病52腸道菌群和I型糖尿病52腸道菌群和II型糖尿病Assessmentandcharacterizationofgutmicrobiotahasbecomeamajorresearchareainhumandisease,includingtype2diabetes,themostprevalentendocrinediseaseworldwide.Tocarryoutanalysisongutmicrobialcontentinpatientswithtype2diabetes,wedevelopedaprotocolforametagenome-wideassociationstudy(MGWAS)andundertookatwo-stageMGWASbasedondeepshotgunsequencingofthegutmicrobialDNAfrom345Chineseindividuals.Weidentifiedandvalidatedapproximately60,000type-2-diabetes-associatedmarkersandstablishedtheconceptofametagenomiclinkagegroup,enablingtaxonomicspecies-levelanalyses.MGWASanalysisshowedthatpatientswithtype2diabeteswerecharacterizedbyamoderatedegreeofgutmicrobialdysbiosis,adecreaseintheabundanceofsomeuniversalbutyrate-producingbacteriaandanincreaseinvariousopportunisticpathogens,aswellasanenrichmentofothermicrobialfunctionsconferringsulphatereductionandoxidativestressresistance.Ananalysisof23additionalindividualsdemonstratedthatthesegutmicrobialmarkersmightbeusefulforclassifyingtype2diabetes.JunjieQin,etal.,Ametagenome-wideassociationstudyofgutmicrobiotaintype2diabetes.Nature490,55–60(04October2012)53腸道菌群和II型糖尿病Assessmentandchar腸道菌群和II型糖尿病JunjieQin,etal.,Ametagenome-wideassociationstudyofgutmicrobiotaintype2diabetes.Nature490,55–60(04October2012)54腸道菌群和II型糖尿病JunjieQin,etal.,菌群紊亂導(dǎo)致炎癥JuneL.RoundandSarkisK.Mazmanian.Thegutmicrobiotashapesintestinalimmuneresponsesduringhealthanddisease.NATUREREVIEWS|IMMUNOLOGY,VOLUME9|MAY2009|313-324.55菌群紊亂導(dǎo)致炎癥JuneL.RoundandSark腸道菌群紊亂引發(fā)的免疫疾病56腸道菌群紊亂引發(fā)的免疫疾病56腸道菌群紊亂導(dǎo)致過敏和炎癥57腸道菌群紊亂導(dǎo)致過敏和炎癥57腸粘膜屏障損傷導(dǎo)致炎癥SilvioBalzan,etal.,Bacterialtranslocation:Overviewofmechanismsandclinicalimpact.JGastro&Hepat22(2007)464–471.58腸粘膜屏障損傷導(dǎo)致炎癥SilvioBalzan,etaIBD發(fā)生機制EamonnM.M.Quigley,GutBacteriainHealthandDisease.Gastro&HepatVol9,9,2013,P560-569.59IBD發(fā)生機制EamonnM.M.Quigley,G致病菌導(dǎo)致IBDINNASEKIROV,etal.,GutMicrobiotainHealthandDisease.PhysiolRev90:859–904,2010;60致病菌導(dǎo)致IBDINNASEKIROV,etal.,SIBO導(dǎo)致腸病INNASEKIROV,etal.,GutMicrobiotainHealthandDisease.PhysiolRev90:859–904,2010;61SIBO導(dǎo)致腸病INNASEKIROV,etal.,腸道菌群對血管疾病的影響KristinaHarris,etal.,IstheGutMicrobiotaaNewFactorContributingtoObesityandItsMetabolicDisorders?JournalofObesity,Volume2012,p1-14.62腸道菌群對血管疾病的影響KristinaHarris,et腸道菌群致動脈粥樣硬化R.Caesar,etal.,Effectsofgutmicrobiotaonobesityandatherosclerosisviamodulationofinflammationandlipidmetabolism.JInternMed2010;268:320–328.63腸道菌群致動脈粥樣硬化R.Caesar,etal.,腸道菌群致癌INNASEKIROV,etal.,GutMicrobiotainHealthandDisease.PhysiolRev90:859–904,2010;64腸道菌群致癌INNASEKIROV,etal.,Gu細菌對免疫和干細胞活動Won-JaeLee.Bacterial-modulatedhostimmunityandstemcellactivationforguthomeostasis.GENES&DEVELOPMENT23:2260–226565細菌對免疫和干細胞活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馬歇爾提出了“腸-肝軸”的概念對腸道和肝臟功能關(guān)系的認識提示新的治療理念,為腸道和肝臟疾病的治療探尋新的治療靶點。98腸-肝軸EamonnM.M.Quigley,Gut腸-肝軸之間的互動腸道菌群失調(diào)，大量G-桿菌繁殖,LPS產(chǎn)生顯著增多腸粘膜屏障功能受損

致病菌和LPS大量移位，經(jīng)門靜脈入肝，損害肝功能。肝功能異常KCs代謝和清除LPS降低，導(dǎo)致腸道功能異常GakuheiSon,etal.,ContributionofGutBacteriatoLiverPathobiology.GastroeResandPrac,Vol2010,ArticleID453563,13pages.99腸-肝軸之間的互動肝功能異常KCs代謝和清除LPS降低，導(dǎo)致腸肝對話100腸肝對話31腸道菌群致非酒精性脂肪肝ValentinaTremaroli&FredrikB?ckhed,Functionalinteractionsbetweenthegutmicrobiotaandhostmetabolism.NATURE|VOL489|13SEPTEMBER2012101腸道菌群致非酒精性脂肪肝ValentinaTremarol腸道菌群導(dǎo)致脂肪肝CarmineFinelliandGiovanniTarantino,NONALCOHOLICFATTYLIVERDISEASE,DIETANDGUTMICROBIOTA.

EXCLIJournal2014;13:461-490102腸道菌群導(dǎo)致脂肪肝CarmineFinelliandG肝臟疾病和SIBO103肝臟疾病和SIBO34腸道菌群與代謝性疾病104腸道菌群與代謝性疾病35腸道菌群增加能量儲存NathalieM.Delzenne&PatriceD.Cani,InteractionBetweenObesityandtheGutMicrobiota:RelevanceinNutrition.Annu.Rev.Nutr.2011.31:15–31.105腸道菌群增加能量儲存NathalieM.Delzenne腸道菌群導(dǎo)致能量聚集PatriceDCaniandNathalieMDelzenne,Interplaybetweenobesityandassociatedmetabolicdisorders:newinsightsintothegutmicrobiota.CurrentOpinioninPharmacology2009,9:737–743.106腸道菌群導(dǎo)致能量聚集PatriceDCaniandN腸道菌群引發(fā)多種代謝疾病107腸道菌群引發(fā)多種代謝疾病381083910940腸道菌群和肥胖110腸道菌群和肥胖41腸道菌群和肥胖是一個新的熱門話題111腸道菌群和肥胖是一個新的熱門話題42肥胖的定義肥胖病一般被定義作為有BMI30以上。體重將近900磅(約400公斤)的里基(RickyNaputi)現(xiàn)年39歲，是世界最重的男子之一。因為體型過于笨重而難以移動，他已經(jīng)在坐落于太平洋關(guān)島的家中躺了五年之久。112肥胖的定義肥胖病一般被定義作為有BMI30以上。體重將肥胖和正常人AmandineEverard&PatriceD.Cani,Diabetes,obesityandgutmicrobiota.BestPractice&ResearchClinicalGastroenterology27(2013)73–83.113肥胖和正常人AmandineEverard&Patri史氏甲烷短桿菌和肥胖為了確定腸道菌群的改變和驗證人體腸道中的乳桿菌或雙歧桿菌是否與肥胖或消瘦相關(guān)，我們采用定量PCR和乳桿菌選擇性培養(yǎng)基分析了68位肥胖志愿者和47位對照的糞便菌群中硬壁菌、擬桿菌、乳酸乳球菌、動物雙歧桿菌和若干乳桿菌種的數(shù)量。結(jié)果：定量PCR試驗中，動物雙歧桿菌(OR=0.63;95%CI0.39-1.01;P=0.056)和史氏甲烷短桿菌(OR=0.76;95%CI0.59-0.97;P=0.03)與正常體重相關(guān)，而羅伊氏乳桿菌(OR=1.79;95%CI1.03-3.10;P=0.04)與肥胖相關(guān)。MillionM,etal.,Obesity-associatedgutmicrobiotaisenrichedinLactobacillusreuterianddepletedinBifidobacteriumanimalisandMethanobrevibactersmithii.IntJObes(Lond).2011Aug9.114史氏甲烷短桿菌和肥胖為了確定腸道菌群的改變和驗證人體腸道中的產(chǎn)甲烷肥胖的人有較高的身體質(zhì)量指數(shù)58人，BMI顯著較高的甲烷陽性者（45.2±2.3公斤/米2）比甲烷陰性（38.5±0.8公斤/米2，P=0.001）。甲烷陽性者也有更大程度的便秘與甲烷相比，陰性者（21.3±6.4比9.5±2.4，P?=.043）。多元回歸分析說明了BMI甲烷之間有顯著的關(guān)系。結(jié)論：這是人類第一次有研究表明，較高濃度的甲烷檢測呼氣測試是預(yù)測顯著更大的肥胖超重者。B.Basseri等，肝臟病雜志胃腸病學(xué)雜志，2012年1月8（1）：22-28美國Cedars-Sinai醫(yī)學(xué)中心115產(chǎn)甲烷肥胖的人有較高的身體質(zhì)量指數(shù)58人，BMI顯著較高的甲腸道菌群致肥胖原因ValentinaTremaroli&FredrikB?ckhed,Functionalinteractionsbetweenthegutmicrobiotaandhostmetabolism.NATURE|VOL489|13SEPTEMBER2012116腸道菌群致肥胖原因ValentinaTremaroli&腸道菌群致肥胖原理JOHNK.DIBAISE,etal.,GutMicrobiotaandItsPossibleRelationshipWithObesity.MayoClinProc.2008;83(4):460-469.117腸道菌群致肥胖原理JOHNK.DIBAISE,eta不同胖瘦人群腸道菌群數(shù)量FabriceArmougom,etal.,MonitoringBacterialCommunityofHumanGutMicrobiotaRevealsanIncreaseinLactobacillusinObesePatientsandMethanogensinAnorexicPatients.PLoSONE4(9):e7125.118不同胖瘦人群腸道菌群數(shù)量FabriceArmougom,腸道菌群和糖尿病119腸道菌群和糖尿病50腸道菌群和I型糖尿病120腸道菌群和I型糖尿病51腸道菌群和I型糖尿病121腸道菌群和I型糖尿病52腸道菌群和II型糖尿病Assessmentandcharacterizationofgutmicrobiotahasbecomeamajorresearchareainhumandisease,includingtype2diabetes,themostprevalentendocrinediseaseworldwide.Tocarryoutanalysisongutmicrobialcontentinpatientswithtype2diabetes,wedevelopedaprotocolforametagenome-wideassociationstudy(MGWAS)andundertookatwo-stageMGWASbasedondeepshotgunsequencingofthegutmicrobialDNAfrom345Chineseindividuals.Weidentifiedandvalidatedapproximately60,000type-2-diabetes-associatedmarkersandstablishedtheconceptofametagenomiclinkagegroup,enablingtaxonomicspecies-levelanalyses.MGWASanalysisshowedthatpatientswithtype2diabeteswerecharacterizedbyamoderatedegreeofgutmicrobialdysbiosis,adecreaseintheabundanceofsomeuniversalbutyrate-producingbacteriaandanincreaseinvariousopportunisticpathogens,aswellasanenrichmentofothermicrobialfunctionsconferringsulphatereductionandoxidativestressresistance.Ananalysisof23addition