腸道菌群和代謝疾病專家講座

腸道菌群與代謝疾病腸道菌群和代謝疾病專家講座第1頁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病：肥胖、糖尿病腸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挑戰(zhàn)和機遇腸道菌群和代謝疾病專家講座第2頁悄悄發(fā)生革命INNASEKIROV,etal.,GutMicrobiotainHealthandDisease.PhysiolRev90:859–904,;腸道菌群和代謝疾病專家講座第3頁一篇值得關(guān)注綜述Naturereviews.Microbiology最新影響因子為22.490()腸道菌群和代謝疾病專家講座第4頁人菌共生KristinaHarris,etal.,IstheGutMicrobiotaaNewFactorContributingtoObesityandItsMetabolicDisorders?JournalofObesity,Volume,p1-14.腸道菌群和代謝疾病專家講座第5頁人腸道菌群種類和數(shù)量EAMONNM.M.QUIGLEYandRODRIGOQUERA,SmallIntestinalBacterialOvergrowth:RolesofAntibiotics,Prebiotics,andProbiotics.GASTROENTEROLOGY;130:S78–S90腸道菌群和代謝疾病專家講座第6頁好細菌和壞細菌腸道菌群和代謝疾病專家講座第7頁菌群是健康關(guān)鍵NathalieM.Delzenne,etal.,Targetinggutmicrobiotainobesity:effectsofprebioticsandprobiotics.Nat.Rev.Endocrinol.7,639–646().腸道菌群和代謝疾病專家講座第8頁腸道菌群對人生理影響腸道菌群和代謝疾病專家講座第9頁腸道菌群-代謝產(chǎn)物-功效JeremyK.Nicholsonetal.,Host-GutMicrobiotaMetabolic.Science336,1262-1267,.腸道菌群和代謝疾病專家講座第10頁影響腸道菌群原因NathalieM.Delzenne&PatriceD.Cani,InteractionBetweenObesityandtheGutMicrobiota:RelevanceinNutrition.Annu.Rev.Nutr..31:15–31.腸道菌群和代謝疾病專家講座第11頁影響腸道菌群原因腸道菌群和代謝疾病專家講座第12頁腸-腦軸/腦-腸軸腸道菌群和代謝疾病專家講座第13頁GermFree(GF)MiceDisplayIncreasedMotorActivityandReducedAnxiety-LikeBehavior.resultssuggestthatthemicrobialcolonizationprocessinitiatessignalingmechanismsthataffectneuronalcircuitsinvolvedinmotorcontrolandanxietybehavior.腸道菌群和代謝疾病專家講座第14頁腸-腦軸概念A(yù)ugustoJ.Montiel-Castro,etal.,Themicrobiota–gut–rainaxis:neurobehavioralcorrelates,healthandsociality.FrontinIntegNeuro.Oct|Vol7|Article70|1-16.腸道菌群和代謝疾病專家講座第15頁腦-腸軸/腸-腦軸：迷走神經(jīng)SueGrenham,etal.,Brain–gut–microbecommunicationinhealthanddisease.FrontiersinPhysio.GastrointSciDecVol2p1-15.腸道菌群和代謝疾病專家講座第16頁腸腦軸/腦腸軸Q.AZIZ,etal.,Gutmicrobiotaandgastrointestinalhealth:currentconceptsandfuturedirections.NeurogastroenterolMotil()25,4–15.腸道菌群和代謝疾病專家講座第17頁菌群影響神經(jīng)功效EamonnM.M.Quigley.Dopatientswithfunctionalgastrointestinaldisordershaveanalteredgutflora?TherAdvGastroenterol()2(Suppl1)S23–S30.腸道菌群和代謝疾病專家講座第18頁菌群紊亂致焦慮和抑郁JaneA.FosterandKaren-AnneMcVeyNeufeld,Gut–brainaxis:howthemicrobiomeinfluencesanxietyanddepression.TrendsinNeurosciences,May,Vol.36,No.5,P305-312腸道菌群和代謝疾病專家講座第19頁精神活動影響腸道菌群JasonA.Hawrelak&StephenP.Myers,TheCausesofIntestinalDysbiosis:AReview.AlternMedRev;9(2):180-197.exposuretopsychologicalstressresultsinasignificantreductionintheproductionofmucinandadecreasedpresenceofacidicmucopolysaccharidesonthemucosalsurface.腸道菌群和代謝疾病專家講座第20頁應(yīng)激/壓力引發(fā)胃腸疾病P.C.KONTUREK,etal.,STRESSANDTHEGUT:PATHOPHYSIOLOGY,CLINICALCONSEQUENCES,DIAGNOSTICAPPROACHANDTREATMENTOPTIONS.JPHYSIO&PHARM,62,6,591-599.腸道菌群和代謝疾病專家講座第21頁腦腸軸紊亂造成潰瘍P.C.KONTUREK,etal.,STRESSANDTHEGUT:PATHOPHYSIOLOGY,CLINICALCONSEQUENCES,DIAGNOSTICAPPROACHANDTREATMENTOPTIONS.JPHYSIO&PHARM,62,6,591-599.腸道菌群和代謝疾病專家講座第22頁應(yīng)激造成IBDP.C.KONTUREK,etal.,STRESSANDTHEGUT:PATHOPHYSIOLOGY,CLINICALCONSEQUENCES,DIAGNOSTICAPPROACHANDTREATMENTOPTIONS.JPHYSIO&PHARM,62,6,591-599.腸道菌群和代謝疾病專家講座第23頁應(yīng)激造成IBSP.C.KONTUREK,etal.,STRESSANDTHEGUT:PATHOPHYSIOLOGY,CLINICALCONSEQUENCES,DIAGNOSTICAPPROACHANDTREATMENTOPTIONS.JPHYSIO&PHARM,62,6,591-599.腸道菌群和代謝疾病專家講座第24頁慢性疲勞與腸-腦軸腸道菌群和代謝疾病專家講座第25頁腸道菌群和代謝疾病專家講座第26頁腸道菌群和自閉癥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,腸道菌群和代謝疾病專家講座第27頁腸-腦軸和自閉癥CarolineG.M.deTheije,etal.,Pathwaysunderlyingthegut-to-brainconnectioninautismspectrumdisordersasfuturetargetsfordiseasemanagement.EuropeanJournalofPharmacology668()S70–S80腸道菌群和代謝疾病專家講座第28頁腸-肝軸EamonnM.M.Quigley,GutBacteriainHealthandDisease.Gastro&HepatVol9,9,,P560-569.1998年馬歇爾提出了“腸-肝軸”概念對腸道和肝臟功效關(guān)系認識提醒新治療理念,為腸道和肝臟疾病治療探尋新治療靶點。腸道菌群和代謝疾病專家講座第29頁腸-肝軸之間互動腸道菌群失調(diào)，大量G-桿菌繁殖,LPS產(chǎn)生顯著增多腸粘膜屏障功效受損

致病菌和LPS大量移位，經(jīng)門靜脈入肝，損害肝功效。肝功效異常KCs代謝和去除LPS降低，造成腸道功效異常GakuheiSon,etal.,ContributionofGutBacteriatoLiverPathobiology.GastroeResandPrac,Vol,ArticleID453563,13pages.腸道菌群和代謝疾病專家講座第30頁腸肝對話腸道菌群和代謝疾病專家講座第31頁腸道菌群致非酒精性脂肪肝ValentinaTremaroli&FredrikB?ckhed,Functionalinteractionsbetweenthegutmicrobiotaandhostmetabolism.NATURE|VOL489|13SEPTEMBER腸道菌群和代謝疾病專家講座第32頁腸道菌群造成脂肪肝CarmineFinelliandGiovanniTarantino,NONALCOHOLICFATTYLIVERDISEASE,DIETANDGUTMICROBIOTA.

EXCLIJournal;13:461-490腸道菌群和代謝疾病專家講座第33頁肝臟疾病和SIBO腸道菌群和代謝疾病專家講座第34頁腸道菌群與代謝性疾病腸道菌群和代謝疾病專家講座第35頁腸道菌群增加能量儲存NathalieM.Delzenne&PatriceD.Cani,InteractionBetweenObesityandtheGutMicrobiota:RelevanceinNutrition.Annu.Rev.Nutr..31:15–31.腸道菌群和代謝疾病專家講座第36頁腸道菌群造成能量聚集PatriceDCaniandNathalieMDelzenne,Interplaybetweenobesityandassociatedmetabolicdisorders:newinsightsintothegutmicrobiota.CurrentOpinioninPharmacology,9:737–743.腸道菌群和代謝疾病專家講座第37頁腸道菌群引發(fā)各種代謝疾病腸道菌群和代謝疾病專家講座第38頁腸道菌群和代謝疾病專家講座第39頁腸道菌群和代謝疾病專家講座第40頁腸道菌群和肥胖腸道菌群和代謝疾病專家講座第41頁腸道菌群和肥胖是一個新熱門話題腸道菌群和代謝疾病專家講座第42頁肥胖定義肥胖病普通被定義作為有BMI30以上。體重快要900磅(約400千克)里基(RickyNaputi)現(xiàn)年39歲，是世界最重男子之一。因為體型過于粗笨而難以移動，他已經(jīng)在坐落于太平洋關(guān)島家中躺了五年之久。腸道菌群和代謝疾病專家講座第43頁肥胖和正常人AmandineEverard&PatriceD.Cani,Diabetes,obesityandgutmicrobiota.BestPractice&ResearchClinicalGastroenterology27()73–83.腸道菌群和代謝疾病專家講座第44頁史氏甲烷短桿菌和肥胖為了確定腸道菌群改變和驗證人體腸道中乳桿菌或雙歧桿菌是否與肥胖或消瘦相關(guān)，我們采取定量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).Aug9.腸道菌群和代謝疾病專家講座第45頁產(chǎn)甲烷肥胖人有較高身體質(zhì)量指數(shù)58人，BMI顯著較高甲烷陽性者（45.2±2.3千克/米2）比甲烷陰性（38.5±0.8千克/米2，P=0.001）。甲烷陽性者也有更大程度便秘與甲烷相比，陰性者（21.3±6.4比9.5±2.4，P?=.043）。多元回歸分析說明了BMI甲烷之間有顯著關(guān)系。結(jié)論：這是人類第一次有研究表明，較高濃度甲烷檢測呼氣測試是預(yù)測顯著更大肥胖超重者。B.Basseri等，肝臟病雜志胃腸病學(xué)雜志，年1月8（1）：22-28美國Cedars-Sinai醫(yī)學(xué)中心腸道菌群和代謝疾病專家講座第46頁腸道菌群致肥胖原因ValentinaTremaroli&FredrikB?ckhed,Functionalinteractionsbetweenthegutmicrobiotaandhostmetabolism.NATURE|VOL489|13SEPTEMBER腸道菌群和代謝疾病專家講座第47頁腸道菌群致肥胖原理JOHNK.DIBAISE,etal.,GutMicrobiotaandItsPossibleRelationshipWithObesity.MayoClinProc.;83(4):460-469.腸道菌群和代謝疾病專家講座第48頁不一樣胖瘦人群腸道菌群數(shù)量FabriceArmougom,etal.,MonitoringBacterialCommunityofHumanGutMicrobiotaRevealsanIncreaseinLactobacillusinObesePatientsandMethanogensinAnorexicPatients.PLoSONE4(9):e7125.腸道菌群和代謝疾病專家講座第49頁腸道菌群和糖尿病腸道菌群和代謝疾病專家講座第50頁腸道菌群和I型糖尿病腸道菌群和代謝疾病專家講座第51頁腸道菌群和I型糖尿病腸道菌群和代謝疾病專家講座第52頁腸道菌群和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(04October)腸道菌群和代謝疾病專家講座第53頁腸道菌群和II型糖尿病JunjieQin,etal.,Ametagenome-wideassociationstudyofgutmicrobiotaintype2diabetes.Nature490,55–60(04October)腸道菌群和代謝疾病專家講座第54頁菌群紊亂造成炎癥JuneL.RoundandSarkisK.Mazmanian.Thegutmicrobiotashapesintestinalimmuneresponsesduringhealthanddisease.NATUREREVIEWS|IMMUNOLOGY,VOLUME9|MAY|313-324.腸道菌群和代謝疾病專家講座第55頁腸道菌群紊亂引發(fā)免疫疾病腸道菌群和代謝疾病專家講座第56頁腸道菌群紊亂造成過敏和炎癥腸道菌群和代謝疾病專家講座第57頁腸粘膜屏障損傷造成炎癥SilvioBalzan,etal.,Bacterialtranslocation:Overviewofmechanismsandclinicalimpact.JGastro&Hepat22