肠道菌群和肥胖PPT课件.ppt

肠道菌群和肥胖,北美医学教育基金会,丁文京博士E-mail:abs94555,12/17/2019,1,肠道菌群和肥胖,12/17/2019,2,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。,12/17/2019,3,肠道菌群和肥胖是一个新的热门话题,12/17/2019,4,肥胖和正常人,AmandineEverard95%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.,12/17/2019,6,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,12/17/2019,7,肠道菌群致肥胖原因,ValentinaTremarolip1-15.,12/17/2019,9,肠道菌群致肥胖原理,JOHNK.DIBAISE,etal.,GutMicrobiotaandItsPossibleRelationshipWithObesity.MayoClinProc.2008;83(4):460-469.,12/17/2019,10,Obesityisassociatedwithphylum-levelchangesinthemicrobiota,reducedbacterialdiversityandalteredrepresentationofbacterialgenesandmetabolicpathways.Theseresultsdemonstratethatadiversityoforganismalassemblagescannonethelessyieldacoremicrobiomeatafunctionallevel,andthatdeviationsfromthiscoreareassociatedwithdifferentphysiologicalstates(obesecomparedwithlean).,12/17/2019,11,双胞胎胖瘦菌群比较,PeterJ.Turnbaugh,etal.,Acoregutmicrobiomeinobeseandleantwins.Nature,Vol457|22January2009|,12/17/2019,12,不同胖瘦人群肠道菌群数量,FabriceArmougom,etal.,MonitoringBacterialCommunityofHumanGutMicrobiotaRevealsanIncreaseinLactobacillusinObesePatientsandMethanogensinAnorexicPatients.PLoSONE4(9):e7125.,12/17/2019,13,不同胖瘦人群肠道菌群种类,FabriceArmougom,etal.,MonitoringBacterialCommunityofHumanGutMicrobiotaRevealsanIncreaseinLactobacillusinObesePatientsandMethanogensinAnorexicPatients.PLoSONE4(9):e7125.,12/17/2019,14,12/17/2019,15,Thegutmicrobiotacompositionhasbeenassociatedwithseveralhallmarksofmetabolicsyndrome(e.g.,obesity,type2diabetes,cardiovasculardiseases,andnon-alcoholicsteatohepatitis).Growingevidencesuggeststhatgutmicrobescontributetotheonsetofthelow-gradeinflammationcharacterisingthesemetabolicdisordersviamechanismsassociatedwithgutbarrierdysfunctions.Recently,enteroendocrinecellsandtheendocannabinoidsystemhavebeenshowntocontrolgutpermeabilityandmetabolicendotoxaemia.Moreover,targetednutritionalinterventionsusingnondigestiblecarbohydrateswithprebioticpropertieshaveshownpromisingresultsinpre-clinicalstudiesinthiscontext,althoughhumaninterventionstudieswarrantfurtherinvestigations.Thesedataunderlinetheadvantageofinvestigatingandchangingthegutmicrobiotaasatherapeutictargetinthecontextofobesityandtype2diabetes.,AmandineEverard457:480484.,12/17/2019,23,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。,12/17/2019,24,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。,12/17/2019,25,Fiaf,fasting-inducedadipocytefactor，禁食脂肪细胞因子,12/17/2019,26,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,12/17/2019,27,影响代谢的因素,基因饮食菌群,12/17/2019,28,肠道菌群影响代谢,FrederikBackhed,ProgrammingofHostMetabolismbytheGutMicrobiota.AnnNutrMetab2011;58(suppl2):4452.,12/17/2019,29,12/17/2019,30,肠道微生态肥胖管理,12/17/2019,31,一项引起世界关注的研究,12/17/2019,32,NCD:正常饮食，HFD:高脂饮食，LB:溶菌肉汤,12/17/2019,33,NaFeiandLipingZhao,Anopportunisticpathogenisolatedfromthegutofanobesehumancausesobesityingermfreemice,TheISMEJournal(2013)7,880884.,12/17/2019,34,12/17/2019,35,12/17/2019,36,12/17/2019,37,12/17/2019,38,12/17/2019,39,12/17/2019,40,12/17/2019,41,12/17/2019,42,12/17/2019,43,12/17/2019,44,12/17/2019,45,12/17/2019,46,12/17/2019,47,12/17/2019,48,Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123-131.,12/17/2019,49,Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123-131.,12/17/2019,50,Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123-131.,12/17/2019,51,聚焦肠道菌群治疗肥胖,Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123-131.,12/17/2019,52,Jia,Wetal.,(2008)Gutmicrobiota:apotentialnewterritoryfordrugtargeting,NatureReviewsDrugDiscovery.7:123