Martin, H.M.; Campbell, B.J.; Hart, C.A.; Williams, H.; Nayar, M.; Colombel, J.-F.; Darfeuille-Michaud, A.; Rhodes, J.M.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA14
Academic Journal
Introduction: There is general consensus that intestinal inflammation in IBD is caused by on abnormal response to the intestinal microflora. It is our hypothesis that the altered mucosol glycosylation seen in IBD could allow mucosal recruitment of otherwise non-pathogenic bacteria and thus cause inflammation. Methods: Mucosa-associated bacteria were isolated from colonoscopic biopsies from CD In = 14), UC (n = 18), and control patients (lBS and sporadic polyps, n = 28) after removal of surface mucus with dithiothrietol. CD ileal-associated E coli were isolated by our French collaborators. Bacteria identified as E coli were screened for possession of known pathogenicity and adhesin genes, agglutination of a panel of human red blood cells, attachment and invasion of, and release of pro-inflammatory cytokines from intestinal cell-lines. Results: 79% (11/14) of CD patients were positive for mucosa-associated bacteria compared with 39% (11/28) of control patients (p = 0.017) and 38% (7/18) of UC patients. Haemagglutinating E coli were identified in 39% (5/14) of CD patients compared with 4% (1/28) of controls (p = 0.01). Agglutination in all cases was inhibited by both soluble p antain fibre and bovine submaxillary mucin (BSM) but not following mild acid hydrolysis of BSM to remove sialic acid/fucose. A range of other carbohydrates and glycoconjugates, including ovine submaxillary mucin were non-inhibitory The agglutinating E coli all possessed at least one adhesin gene but lacked conventional virulence genes of pathogenic E coil Of the CD ileal-associated E coli, one strain, LF10, was shown, using both haemagglutination and PCR, to possess an adhesin specific for M blood group antigen. All agglutinating E coli were shown to adhere to both HT29 and 1407 cell lines, inducing release of the pro-inflammatory cytokine IL-8 up to 4-fold above baseline levels (p < 0.01), but not IL-1B. Conclusions: CD is associated with an increased prevalence of mucosally associated E...


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