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TheEffectofDietontheHumanGutMicrobiome:AMetagenomicAnalysisinHumanizedGnotobioticMice汇报人：李博磊导师：程磊副教授转化医学（TranslationalMedicine）:是指一类医学研究，能够很好地将基础研究与解决患者实际问题结合起来，将基础研究的成果“转化”为实际患者的疾病预防、诊断和治疗及预后评估。IF≈14Theauthor•PeterJ.Turnbaugh•CenterforGenomeSciences,WashingtonUniversitySchoolofMedicine•Researchfield:gutmicrobiomeandobesity•TurnbaughPJetal.(2006).Anobesity-associatedgutmicrobiomewithincreasedcapacityforenergyharvest.Nature444(7122):1027-1031•TurnbaughPJetal.(2008).Diet-inducedobesityislinkedtomarkedbutreversiblealterationsinthemousedistalgutmicrobiome.Cellhostµbe3(4):213-223.•TurnbaughPJetal.(2009).Thecoregutmicrobiome,energybalanceandobesity.TheJournalofphysiology587(Pt17):4153-4158.•TurnbaughPJetal.(2009).Acoregutmicrobiomeinobeseandleantwins.Nature457(7228):480-484.BackgroundHowdoestheideacomeout？→Previousstudy:•Familymembershadamoresimilarcommunitystructurethanunrelatedindividuals.•Thedegreeofrelatednessofthefecalmicrobiotaofadultmonozygotictwinpairswasnotgreaterthanthatofdizygotictwinpairs.Whywechosethehumanizedgnotobioticanimalsastheresearchobject?•anumerousuncontrolledvariables,bothgeneticandenvironmental→gnotobioticanimals（controllinghostgenotype,microbialcommunitycomposition,diet,andhousingconditions，howevermostbacterialgeneraandspeciesfoundinmicearenotseeninhumans）→HumanizedGnotobioticMiceTurnbaughPJetal.(2009).Acoregutmicrobiomeinobeseandleantwins.Nature457(7228):480-484.Design•Establishmentofahumanizedmousegutmicrobiota•Propagationofthehumanizedmousegutmicrobiota•Establishmentofahumanizedmousegutmicrobiotafromfrozensamples•Temporalandspatialfeaturesofthehumangutmicrobiota•Microbialtransmissionofadiposity•Thehumanizedmousegutmicrobiome•TranscriptionalresponsesofthemicrobiometodietshiftsMethod1.EstablishmentofahumanizedmousegutmicrobiotaEstablishment;Westerndiet:high-fat,high-sugarVSLF/PPdiet:low-fat,plantpolysaccharide–richdietResult•EstablishmentofahumanizedmousegutmicrobiotafromfrozensamplesMethod•Propagationofthehumanizedmousegutmicrobiotawhetherthehumanizedmousemicrobiotacouldbetransmittedtoasecondgenerationofanimals;legacyeffectsVSdietResult•PropagationofthehumanizedmousegutmicrobiotaMethod•EstablishmentofahumanizedmousegutmicrobiotafromfrozensamplesfrozensampleResult1.EstablishmentofahumanizedmousegutmicrobiotaMethod•TemporalandspatialfeaturesofthehumangutmicrobiotaTemporalandspatialResult•TemporalfeaturesofthehumangutmicrobiotaResult•SpatialfeaturesofthehumangutmicrobiotaMethod•MicrobialtransmissionofadiposityLF/PPdietVSwesterndietLF/PPmice’smicrobiaVSwesternmice’smicrobia2weeks，samedietLF/PPmice’smicrobia→GFmiceobesitywesternmice’smicrobial→GFmiceobisityResult•MicrobialtransmissionofadiposityMethod•ThehumanizedmousegutmicrobiomeResultMethod•TranscriptionalresponsesofthemicrobiometodietshiftsResultMethod•Transcriptionalresponsesofthemicrobiometodietshiftscecalcontent→culture→Restrictionfragmentlengthpolymorphismscreening：identifyfourisolatesbelongingtoErysipelotrichi→sequence：oneoftheisolatesshared98%identitywiththe16SrRNAgeneofC.innocuumATCC14501→comparedmessengerRNAs(mRNAs)expressedbythegenesrepresentedintheC.innocuumgenomeintheLF/PPdiet–associatedversusWesterndiet–associatedcecalmicrobiotaResultTranscriptionalresponsesofthemicrobiometodietshiftsDiscussion•实验总结：1.模型建立成功2.肠道菌群向子代传播3.微生态结构根据肠道不同位置变化4.从菌群、基因、mRNA水平阐述了饮食对肠道微生态的改变Discussion•转化医学：1.通过无菌鼠模型，帮助临床宏基因组研究2.再现益生菌3.对人施加饮食干预时，可以不需要很长时间4.猜测：小鼠和人有很多相似之处还未被发觉Discussion•下一步研究方向：1.饮食为什么能够对微生态结构产生如此大的变化？2.创建更为个性化的模型3.菌群可以传至下一代，是否可以解释“一些只持续在少数几代的遗传现象”？short-termheritableinfluences个人感悟1.转化医学的观念：紧密将实验室研究、动物实验、临床问题结合，来设计实验2.动物实验在设计时，可以多加一些研究点进去，增加广度3.实验设计中适当加入更深入（机制）研究，增加深度4.无菌鼠在口腔微生物研究领域的使用，是机遇也是挑战无菌鼠可以复制出人肠道微生态，是否也可以复制出人口腔微生态呢？？请老师批评指正谢谢！