肠道菌群与代谢疾病.ppt

肠道菌群与代谢疾病,目录,肠道菌群与健康和疾病概述肠-脑轴肠-肝轴肠道菌群与代谢性疾病：肥胖、糖尿病肠道菌群与肠病肠道菌群与免疫肠道菌群与其它疾病革命带来的挑战和机遇,悄悄发生的革命,INNASEKIROV,etal.,GutMicrobiotainHealthandDisease.PhysiolRev90:859904,2010;,一篇值得关注的综述,Naturereviews.Microbiology最新的影响因子为22.490(2013),人菌共生,KristinaHarris,etal.,IstheGutMicrobiotaaNewFactorContributingtoObesityandItsMetabolicDisorders?JournalofObesity,Volume2012,p1-14.,人肠道菌群种类和数量,EAMONNM.M.QUIGLEYandRODRIGOQUERA,SmallIntestinalBacterialOvergrowth:RolesofAntibiotics,Prebiotics,andProbiotics.GASTROENTEROLOGY2006;130:S78S90,好细菌和坏细菌,菌群是健康的核心,NathalieM.Delzenne,etal.,Targetinggutmicrobiotainobesity:effectsofprebioticsandprobiotics.Nat.Rev.Endocrinol.7,639646(2011).,肠道菌群对人生理的影响,肠道菌群-代谢产物-功能,JeremyK.Nicholsonetal.,Host-GutMicrobiotaMetabolic.Science336,1262-1267,2012.,影响肠道菌群的因素,NathalieM.Delzenne13:461-490,肝脏疾病和SIBO,肠道菌群与代谢性疾病,肠道菌群增加能量储存,NathalieM.Delzenne95%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.,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,肠道菌群致肥胖原因,ValentinaTremaroli83(4):460-469.,不同胖瘦人群肠道菌群数量,FabriceArmougom,etal.,MonitoringBacterialCommunityofHumanGutMicrobiotaRevealsanIncreaseinLactobacillusinObesePatientsandMethanogensinAnorexicPatients.PLoSONE4(9):e7125.,肠道菌群和糖尿病,肠道菌群和I型糖尿病,肠道菌群和I型糖尿病,肠道菌群和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.Nature490,5560(04October2012),肠道菌群和II型糖尿病,JunjieQin,etal.,Ametagenome-wideassociationstudyofgutmicrobiotaintype2diabetes.Nature490,5560(04October2012),菌群紊乱导致炎症,JuneL.RoundandSarkisK.Mazmanian.Thegutmicrobiotashapesintestinalimmuneresponsesduringhealthanddisease.NATUREREVIEWS|IMMUNOLOGY,VOLUME9|MAY2009|313-324.,肠道菌群紊乱引发的免疫疾病,肠道菌群紊乱导致过敏和炎症,肠粘膜屏障损伤导致炎症,SilvioBalzan,etal.,Bacterialtranslocation:Overviewofmechanismsandclinicalimpact.JGastro,SIBO导致肠病,INNASEKIROV,etal.,GutMicrobiotainHealthandDisease.PhysiolRev90:859904,2010;,肠道菌群对血管疾病的影响,KristinaHarris,etal.,IstheGutMicrobiotaaNewFactorContributingtoObesityandItsMetabolicDisorders?JournalofObesity,Volume2012,p1-14.,肠道菌群致动脉粥样硬化,R.Caesar,etal.,Effectsofgutmicrobiotaonobesityandatherosclerosisviamodulationofinflammationandlipidmetabolism.JInternMed2010;268:320328.,肠道菌群致癌,INNASEKIROV,etal.,GutMicrobiotainHealthandDisease.