Microbial etiology of Inflammatory Bowel Disease: Microbial diversity and the role of Escherichia coli

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dc.contributor.authorSEPEHRI, SHADI
dc.contributor.examiningcommitteeAlfa, Michelle (Medical Microbiology) Rodriguez-Lecompte, Juan Carlos (Animal Sciences)Sartor, Balfour (Medical Microbiology and Immunology, University of North Carolina School of Medicine)en
dc.contributor.supervisorKrause, Denis (Animal Sciences)en
dc.date.accessioned2010-04-12T18:26:18Z
dc.date.available2010-04-12T18:26:18Z
dc.date.issued2010-04-12T18:26:18Z
dc.degree.disciplineMedical Microbiologyen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractInflammatory bowel disease (IBD), comprises Crohn’s disease (CD) and ulcerative colitis (UC), and is a chronic relapsing inflammation of gastrointestinal tract without any known cause or cure. Currently, it is accepted that IBD is a result of a dysfunctional immune response to commensal bacteria in a genetically susceptible host, and that environmental factors can trigger the onset or reactivation of the disease. This thesis considers the possibility of a specific pathogenic agent as well as an imbalance in the composition of the normal microflora in the pathogenesis of IBD. Gut biopsy tissues were taken from a population-based case-control tissue bank held at the University of Manitoba. Automated ribosomal intergenic spacer analysis (ARISA) and terminal restriction fragment length polymorphisms (T-RFLP) were employed to assess the diversity of gut microbiota. The phylogenetic, virulence and biochemical characteristics of Escherichia coli isolated from IBD biopsies were examined using multi-locus sequence typing (MLST), DNA microarray technology and API 20E system. Utilizing ARISA and T-RFLP, a remarkable increase in the order of unclassified Clostridia was detected in inflamed tissues, particularly in CD patients (P < 0.05). Moreover, species richness and diversity were the highest in non-inflamed IBD biopsies. Culture-based quantification detected a significantly higher number of E. coli in IBD tissues (P < 0.05). Phylogenetic analysis revealed the tendency of E. coli isolated from IBD patients to be grouped into separate clonal clusters based on their allelic profiles (P = 0.02). A link was detected between uropathogenic E. coli (UPEC) CFT073 and strains isolated from IBD, with regards to gene distribution and virulence, using microarray technology. Amino acid substitutions N91S and S99N in FimH, the adhesive subunit of E. coli type I fimbria, were significantly associated to IBD (P < 0.05). This study demonstrated an increase in the microbial diversity of non-inflamed IBD tissues and suggested a recruitment phase of bacterial adherence and colonization, before the inflammation sets in. Furthermore, E. coli isolated from IBD tissues were distinct from commensal strains in both clonal and virulence characteristics and shared remarkable traits with extraintestinal pathogenic E. coli. Features involved in bacterial adhesion to epithelial cells may hold the key to E. coli pathogenesis in IBD.en
dc.description.noteMay 2010en
dc.format.extent1261294 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.citationKotlowski R, Bernstein CN, Sepehri S and Krause DO. 2007. High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut;56;669-675.[URL: http://gut.bmj.com/content/56/5/669.abstract]en
dc.identifier.citationSepehri S, Kotlowski R, Bernstein CN, and Krause DO. 2007. Microbial diversity of inflamed and non-inflamed gut biopsy tissues in inflammatory bowel disease. Inflamm Bowel Dis;13:675-683.[URL: http://www3.interscience.wiley.com/journal/114099828/abstract]en
dc.identifier.citationSepehri S, Kotlowski R, Bernstein CN, and Krause DO. 2009. Phylogenetic analysis of inflammatory bowl disease associated Escherichia coli and the FimH virulence determinant. Inflamm Bowel Dis;15:1737–1745.[URL: http://www3.interscience.wiley.com/journal/122400027/abstract]en
dc.identifier.urihttp://hdl.handle.net/1993/3977
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectInflammatory Bowel Diseaseen
dc.subjectCrohn's Diseaseen
dc.subjectUlcerative colitisen
dc.subjectMicrobial diversityen
dc.subjectEscherichia colien
dc.subjectMLSTen
dc.subjectARISAen
dc.subjectT-RFLPen
dc.subjectMicroarray gene contenten
dc.subjectVirulence factorsen
dc.subjectPhylogenetic analysisen
dc.subjectfimHen
dc.subjectAIECen
dc.subjectUPECen
dc.subjectAPECen
dc.subjectNissle 1917en
dc.titleMicrobial etiology of Inflammatory Bowel Disease: Microbial diversity and the role of Escherichia colien
dc.typedoctoral thesisen_US
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