肠道菌群和肥胖课件

肠道菌群和肥胖北美医学教育基金会丁文京博士E-mail:肠道菌群和肥胖北美医学教育基金会丁文京博士1肠道菌群和肥胖肠道菌群和肥胖2肥胖的定义肥胖病一般被定义作为有BMI30以上。体重将近900磅(约400公斤)的里基(RickyNaputi)现年39岁，是世界最重的男子之一。因为体型过于笨重而难以移动，他已经在坐落于太平洋关岛的家中躺了五年之久。肥胖的定义肥胖病一般被定义作为有BMI30以上。体重将3肠道菌群和肥胖是一个新的热门话题肠道菌群和肥胖是一个新的热门话题4肥胖和正常人AmandineEverard&PatriceD.Cani,Diabetes,obesityandgutmicrobiota.BestPractice&ResearchClinicalGastroenterology27(2013)7383.肥胖和正常人AmandineEverard&Patri5史氏甲烷短杆菌和肥胖为了确定肠道菌群的改变和验证人体肠道中的乳杆菌或双歧杆菌是否与肥胖或消瘦相关，我们采用定量PCR和乳杆菌选择性培养基分析了68位肥胖志愿者和47位对照的粪便菌群中硬壁菌、拟杆菌、乳酸乳球菌、动物双歧杆菌和若干乳杆菌种的数量。结果：定量PCR试验中，动物双歧杆菌(OR=0.63;95%CI0.39-1.01;P=0.056)和史氏甲烷短杆菌(OR=0.76;95%CI0.59-0.97;P=0.03)与正常体重相关，而罗伊氏乳杆菌(OR=1.79;95%CI1.03-3.10;P=0.04)与肥胖相关。MillionM,etal.,Obesity-associatedgutmicrobiotaisenrichedinLactobacillusreuterianddepletedinBifidobacteriumanimalisandMethanobrevibactersmithii.IntJObes(Lond).2011Aug9.史氏甲烷短杆菌和肥胖为了确定肠道菌群的改变和验证人体肠道中的6产甲烷肥胖的人有较高的身体质量指数58人，BMI显着较高的甲烷阳性者（45.22.3公斤/米2）比甲烷阴性（38.50.8公斤/米2，P=0.001）。甲烷阳性者也有更大程度的便秘与甲烷相比，阴性者（21.36.4比9.52.4，P?=.043）。多元回归分析说明了BMI甲烷之间有显着的关系。结论：这是人类第一次有研究表明，较高浓度的甲烷检测呼气测试是预测显着更大的肥胖超重者。B.Basseri等，肝脏病杂志胃肠病学杂志，2012年1月8（1）：22-28美国Cedars-Sinai医学中心产甲烷肥胖的人有较高的身体质量指数58人，BMI显着较高的甲7肠道菌群致肥胖原因ValentinaTremaroli&FredrikBckhed,Functionalinteractionsbetweenthegutmicrobiotaandhostmetabolism.NATURE|VOL489|13SEPTEMBER2012肠道菌群致肥胖原因ValentinaTremaroli&8肠道菌群致肥胖原理GiulioGMuccioli,etal.,Theendocannabinoidsystemlinksgutmicrobiotatoadipogenesis.MolecularSystemsBiology6:392;p1-15.肠道菌群致肥胖原理GiulioGMuccioli,et9肠道菌群致肥胖原理JOHNK.DIBAISE,etal.,GutMicrobiotaandItsPossibleRelationshipWithObesity.MayoClinProc.2008;83(4):460-469.肠道菌群致肥胖原理JOHNK.DIBAISE,eta10Obesityisassociatedwithphylum-levelchangesinthemicrobiota,reducedbacterialdiversityandalteredrepresentationofbacterialgenesandmetabolicpathways.Theseresultsdemonstratethatadiversityoforganismalassemblagescannonethelessyieldacoremicrobiomeatafunctionallevel,andthatdeviationsfromthiscoreareassociatedwithdifferentphysiologicalstates(obesecomparedwithlean).Obesityisassociatedwithphy11双胞胎胖瘦菌群比较PeterJ.Turnbaugh,etal.,Acoregutmicrobiomeinobeseandleantwins.Nature,Vol457|22January2009|双胞胎胖瘦菌群比较PeterJ.Turnbaugh,e12不同胖瘦人群肠道菌群数量FabriceArmougom,etal.,MonitoringBacterialCommunityofHumanGutMicrobiotaRevealsanIncreaseinLactobacillusinObesePatientsandMethanogensinAnorexicPatients.PLoSONE4(9):e7125.不同胖瘦人群肠道菌群数量FabriceArmougom,13不同胖瘦人群肠道菌群种类FabriceArmougom,etal.,MonitoringBacterialCommunityofHumanGutMicrobiotaRevealsanIncreaseinLactobacillusinObesePatientsandMethanogensinAnorexicPatients.PLoSONE4(9):e7125.不同胖瘦人群肠道菌群种类FabriceArmougom,14肠道菌群和肥胖课件15Thegutmicrobiotacompositionhasbeenassociatedwithseveralhallmarksofmetabolicsyndrome(e.g.,obesity,type2diabetes,cardiovasculardiseases,andnon-alcoholicsteatohepatitis).Growingevidencesuggeststhatgutmicrobescontributetotheonsetofthelow-gradeinflammationcharacterisingthesemetabolicdisordersviamechanismsassociatedwithgutbarrierdysfunctions.Recently,enteroendocrinecellsandtheendocannabinoidsystemhavebeenshowntocontrolgutpermeabilityandmetabolicendotoxaemia.Moreover,targetednutritionalinterventionsusingnondigestiblecarbohydrateswithprebioticpropertieshaveshownpromisingresultsinpre-clinicalstudiesinthiscontext,althoughhumaninterventionstudieswarrantfurtherinvestigations.Thesedataunderlinetheadvantageofinvestigatingandchangingthegutmicrobiotaasatherapeutictargetinthecontextofobesityandtype2diabetes.AmandineEverard&PatriceD.Cani,Diabetes,obesityandgutmicrobiota.BestPractice&ResearchClinicalGastroenterology27(2013)7383.Thegutmicrobiotacomposition16肠道菌群致代谢紊乱机理ThomasGreinerandFredrikBackhed.Effectsofthegutmicrobiotaonobesityandglucosehomeostasis.TrendsinEndocrinologyandMetabolism,April2011,Vol.22,No.4recentdatahaverevealedthatthegutmicrobiotacanaffectobesity.Thegutmicrobiotacontributestohostmetabolismbyseveralmechanismsincludingincreased energy harvest from the diet,modulation of lipid metabolism,altered endocrine function,and increased inflammatory tone.Thegutmicrobiotacouldthusbeconsideredtobeanenvironmentalfactorthatmodulatesobesityandothermetabolicdiseases.肠道菌群致代谢紊乱机理ThomasGreinerand17肠道菌群致肥胖-糖尿病机理PatriceD.Cani,etal.,Involvementofgutmicrobiotainthedevelopmentoflow-gradeinflammationandtype2diabetesassociatedwithobesity.GutMicrobes3:4,279-288.肠道菌群致肥胖-糖尿病机理PatriceD.Cani,e18无菌鼠定植后代谢路径EmidioScarpellini,etal.,Gutmicrobiotaandobesity.InternEmergMed(2010)5(Suppl1):S53S56.无菌鼠定植后代谢路径EmidioScarpellini,19肠道菌群和肥胖课件20越来越多的证据表明肠道菌群与肥胖、膜岛素抵抗等代谢性疾病的发生密切相关，具体分子机制也正被逐步揭示出来。肠道菌群不仅可调节能量代谢，促进脂肪过度积累，还是宿主全身性低度慢性炎症和膜岛素抵抗等代谢紊乱的诱发因素之一。肠道菌群有可能成为预防和治疗肥胖症的新靶点。赵立平和费娜，肠道菌群与肥胖症的关系研究进展，微生物与感染2013,8(2)67-71越来越多的证据表明肠道菌群与肥胖、膜岛素抵抗等代谢性疾病的发21菌群和肥胖菌群和肥胖22胖人肠道菌群多样化少TurnbaughPJ,etal.Acoregutmicrobiomeinobeseandleantwins.Nature2009;457:480484.胖人肠道菌群多样化少TurnbaughPJ,etal.23菌群和肥胖小老鼠研究：母亲和子代之间、子代（亲/表兄弟姐妹）之间的盲肠微生物区系各都具有相似的结构组成，而无血缘关系的两个小鼠家族之间的盲肠微生物区系在属的水平上却有显著差异。菌群和肥胖小老鼠研究：24肠道菌群和肥胖肥胖基因（ob基因），其突变也引起小鼠肠道优势微生物类群比例的显著变化，并可能导致脂肪贮积和肥胖。肠道菌群和肥胖肥胖基因（ob基因），其突变也引起小鼠肠道优势25Fiaffasting-inducedadipocytefactor，禁食脂肪细胞因子Fiaffasting-inducedadipocyte26人体内的细菌相比进食的多少而言，可能是导致肥胖的一个更重要的因素人体内的细菌相比进食的多少而言，可能是导致肥胖的一个更重要的27影响代谢的因素基因饮食菌群影响代谢的因素基因28肠道菌群影响代谢FrederikBackhed,ProgrammingofHostMetabolismbytheGutMicrobiota.AnnNutrMetab2011;58(suppl2):4452.肠道菌群影响代谢FrederikBackhed,Prog29肠道菌群和肥胖课件30肠道微生态肥胖管理肠道微生态肥胖管理31一项引起世界关注的研究一项引起世界关注的研究32NCD:正常饮食，HFD:高脂饮食，LB:溶菌肉汤NCD:正常饮食，HFD:高脂饮食，LB:溶菌肉汤33NaFeiandLipingZhao,Anopportunisticpathogenisolatedfromthegutofanobesehumancausesobesityingermfreemice,TheISMEJournal(2013)7,880884.NaFeiandLipingZhao,Anop34肠道菌群和肥胖课件35肠道菌群和肥胖课件36肠道菌群和肥胖课件37肠道菌群和肥胖课件38肠道菌群和肥胖课件39肠道菌群和肥胖课件40肠道菌群和肥胖课件41肠道菌群和肥胖课件42肠道菌群和肥胖课件43肠道菌群和肥胖课件44肠道菌群和肥胖课件45肠道菌群和肥胖课件46肠道菌群和肥胖课件47肠道菌群和肥胖课件48Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123-131.Jia,Wetal.,(2008)Gutmic49Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123-131.Jia,Wetal.,(2008)Gutmic50Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123-131.Jia,Wetal.,(2008)Gutmic51聚焦肠道菌群治疗肥胖Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123-131.聚焦肠道菌群治疗肥胖Jia,Wetal.,(20052Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123-131.Jia,Wetal.,(2008)Gutmic53肠道菌群和肥胖课件54肠道菌群和肥胖课件55肠道菌群和肥胖课件56肠道菌群和肥胖课件57p经常不断地学习,你就什么都知道。你知道得越多,你就越有力量pStudyConstantly,AndYouWillKnowEverything.TheMoreYouKnow,TheMorePowerfulYouWillBe写在最后经常不断地学习,你就什么都知道。你知道得越多,你就越有力量写58谢谢大家荣幸这一路，与你同行ItSAnHonorToWalkWithYouAllTheWay演讲人：XXXXXX时 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