Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA 英文参考文献.docVIP

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Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA 英文参考文献.doc

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Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA 英文参考文献

PatientswithInflammatoryBowelDiseaseExhibit DysregulatedResponsestoMicrobialDNA NaomiS.C.Hotte,SaadY.Salim,RobertH.Tso,EricJ.Albert,PhilBach,JohnWalker, LevinusA.Dieleman,RichardN.Fedorak,KarenL.Madsen* DepartmentofMedicine,UniversityofAlberta,Edmonton,Alberta,Canada Abstract Background:Acriticalroleforthegutepitheliumliesinitsabilitytodiscriminatebetweenpathogensandcommensalsand respond appropriately. Dysfunctional interactions between microbes and epithelia are believed to have a role in inflammatoryboweldisease(IBD).Inthisstudy,weanalyzedmicrobiotaandgeneexpressioninIBDpatientsandexamined responsesofmucosalbiopsiestobacterialDNA. Methods:Biopsiesweretakenfromnon-inflamedareasofthecoloninhealthycontrols(HC)andCrohn’sdisease(CD)and ulcerativecolitis(UC)patientsinremission.Biopsiesweresnap-frozenorculturedwithDNAfromLactobacillusplantarum (LP) or Salmonella dublin (SD). Gene expression was analyzed under basal conditions and in response to DNA. Gene networks were analyzed using Ingenuity Pathways software.Mucosal-associated microbiota was analyzed using terminal restrictionfragmentlengthpolymorphism.FrequencyofsinglenucleotidepolymorphismsinNOD2andTLR9wasassessed. Results:PatientswithIBDhadalteredmicrobiota,enhancedexpressionofinflammatorygenes,andincreasedcorrelations between specific gene expression and microbes. Principle component analysis showed CD and UC patients to cluster independently from healthy controls in both gene expression and microbial analysis. DNA from LP stimulated anti- inflammatorypathwaysincontrolsandUCpatients,butinducedanupregulationofIL17AinCDpatients.Therewereno differencesinSNPfrequenciesofTLR9orNOD2inthegroups. Conclusions:PatientswithCrohn’sdiseaseexhibitalteredresponsestobacterialDNA.Thesefindingssuggestthatthegut responsetobacterialDNAmaydependnotonlyonthespecifictypeofbacterialDNA,butalsoonthehost. Citation:HotteNSC,SalimSY,TsoRH,AlbertEJ,BachP,etal.(2012)PatientswithInflammatoryBowelDiseaseExhibitDysregulatedResponsestoMicrobial D