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,particula rly Escherichia coli, in these conditions. Methods:Mucosa-associated bacteria w ere isolated, after dithiothreitol mucolysis, from biopsy samples obtained at co lonoscopy(Crohn’s disease, n = 14 patients; ulcerative colitis, n = 21;noninfla med controls, n = 24) and at surgical resection (colon cancer, n = 21). Intramuc osal bacteria were grown after gentamicin treatment followed by hypotonic lysis. Results:Mucosa-associated and intramucosal bacteria were cultured more commonl y in Crohn’s disease (79%, P = 0.03; and 71%,P < 0.01, respectively), but not ulcerative colitis (38%and48%), than in noninflamed controls (42%and 29%) a nd 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 diseas e (6/14; 43%) than in noninflamed controls (4/24, 17%), as also were intramuco sal E. coli: Crohn’s disease, 29%; controls, 9%. E. coli expressed hemaggluti nins in 39%of Crohn’s cases and 38%of cancers but only 4%of controls, and th is correlated (P = 0.01) with adherence to the I407 and HT29 cell lines. Invasio n was cell-line dependent. E. coli, including nonadherent isolates, induced int erleukin-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. Concl usions: 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. 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, particularised in Escherichia coli, in these conditions. Methods: Mucosa-associated bacteria w ere isolated, after dithiothreitol mucolysis, from biopsy samples obtained at co lonoscopy (Crohn’s disease, n = 14 patients; ulcerative colitis, n = 21; noninfla med controls, n = 24) and at surgical resection (colon cancer, n = 21). Intramuc osal bacteria were grown after gentamicin treatment followed by hypotonic lysis. Results: Mucosa-associated and intramucosal bacteria were cultured more common il y in Crohn’s disease (79%, P = 0.03; and 71%, P <0.01, respectively), but not Mucosa-associated E. coli, which accounted for 53% of isolates (42% and 29%) a nd were commonly cultured from colon cancers (71% and 57% , were m coli common in Crohn’s diseas e (6/14; 43%) than in noninflamed controls (4/24, 17%), as also were intramuco sal E. coli: Crohn’s disease, 29%; controls, 9% expressed hemagglutin nins in 39% of Crohn’s cases and 38% of cancers but only 4% of controls, and th is correlated (P = 0.01) with adherence to the I407 and HT29 cell lines. coli, including nonadherent isolates, induced int erleukin-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. Concl usions: 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.