Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer

Abstract

Background & Aims: Altered mucosal glycosylation in inflammatory bowel disease and colon cancer could affect mucosal bacterial adherence. This study aimed to quantify and characterize mucosa-associated and intramucosal bacteria, particularly Escherichia coli, in these conditions. Methods: Mucosa-associated bacteria were isolated, after dithiothreitol mucolysis, from biopsy samples obtained at colonoscopy (Crohn’s disease, n = 14 patients; ulcerative colitis, n = 21; noninflamed controls, n = 24) and at surgical resection (colon cancer, n = 21). Intramucosal bacteria were grown after gentamicin treatment followed by hypotonic lysis. Results: Mucosa-associated and intramucosal bacteria were cultured more commonly in Crohn’s disease (79%, P = 0.03; and 71%, P < 0.01, respectively), but not ulcerative colitis (38% and 48%), than in noninflamed controls (42% and 29%) and were commonly cultured from colon cancers (71% and 57%). Mucosa-associated E. coli, which accounted for 53% of isolates, were more common in Crohn’s disease (6/14; 43%) than in noninflamed controls (4/24, 17%), as also were intramucosal E. coli: Crohn’s disease, 29%; controls, 9%. E. coli expressed hemagglutinins in 39% of Crohn’s cases and 38% of cancers but only 4% of controls, and this correlated ( P = 0.01) with adherence to the I407 and HT29 cell lines. Invasion was cell-line dependent. E. coli, including nonadherent isolates, induced interleukin-8 release from the cell lines. E. coli adhesins showed no blood group specificity, excepting 1 cancer isolate (HM44) with specificity for the Thomsen-Friedenreich antigen, but they could be blocked by soluble plantain fiber. Conclusions: These studies support a central role for mucosally adherent bacteria in the pathogenesis of Crohn’s disease and colon cancer. Soluble plant fibers that inhibit their adherence have therapeutic potential.