Site and Strain-Specific Variation in Gut Microbiota Profiles and Metabolism in Experimental Mice 英文参考文献.docVIP

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Site and Strain-Specific Variation in Gut Microbiota Profiles and Metabolism in Experimental Mice 英文参考文献.doc

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Site and Strain-Specific Variation in Gut Microbiota Profiles and Metabolism in Experimental Mice 英文参考文献

SiteandStrain-SpecificVariationinGutMicrobiota ProfilesandMetabolisminExperimentalMice MelissaK.Friswell1,HelenGika3,4,IanJ.Stratford2,GeorgiosTheodoridis3,4,BrianTelfer2,IanD. Wilson3,AndrewJ.McBain1* 1MicrobiologyResearchGroup,SchoolofPharmacyandPharmaceuticalSciences,TheUniversityofManchester,Manchester,UnitedKingdom,2ExperimentalOncology ResearchGroup,SchoolofPharmacyandPharmaceuticalSciences,TheUniversityofManchester,Manchester,UnitedKingdom, 3AstraZeneca,DepartmentofClinical Pharmacology, Drug Metabolism and Pharmacokinetics, Macclesfield, United Kingdom, 4Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece Abstract Background:Thegastrointestinaltractmicrobiota(GTM)ofmammalsisacomplexmicrobialconsortium,thecomposition and activities of which influences mucosal development, immunity, nutrition and drug metabolism. It remains unclear whetherthecompositionofthedominantGTMisconservedwithinanimalsofthesamestrainandwhetherstableGTMsare selectedforbyhost-specificfactorsordictatedbyenvironmentalvariables. Methodology/PrincipalFindings:TheGTMcompositionofsixhighlyinbred,geneticallydistinctstrainsofmouse(C3H,C57, GFEC,CD1,CBAnu/nuandSCID)wasprofiledusingeubacterial–specificPCR-DGGEandquantitativePCRoffeces.Animals exhibitedstrain-specificfecaleubacterialprofilesthatwerehighlystable(c..95%concordanceover26monthsforC57). Analyses of mice that had been relocated before and after maturity indicated marked, reproducible changes in fecal consortiaandthatoccurredonlyinyounganimals.ImplantationofafemaleBDF1mousewithgeneticallydistinct(C57and Agoutie)embryosproducedhighlysimilarGTMprofiles(c.95%concordance)betweenmotherandoffspring,regardlessof offspring strain, which was also reflected in urinary metabolite profiles. Marked institution-specific GTM profiles were apparentinC3Hmiceraisedintwodifferentresearchinstitutions. Conclusion/Significance:Strain-specificdataweresuggestiveofgeneticdeterminationofthecompositionandactivitiesof intesti