Colonization of the Human Gut by E. coli and Colorectal Cancer Risk

M. Bonnet, E. Buc, P. Sauvanet, C. Darcha, D. Dubois, B. Pereira, P. Dechelotte, R. Bonnet, D. Pezet, A. Darfeuille-Michaud
2013 Clinical Cancer Research  
Purpose: The intestinal microbiota is potentially involved in the development of colorectal carcinoma via various mechanisms. Escherichia coli are commensal bacteria of the human gut microbiota, but some pathogenic strains have acquired the ability to induce chronic inflammation and/or produce toxins, such as cyclomodulin, which could participate in the carcinogenesis process. Here, we analyzed the E. coli population associated with mucosa of patients with colon cancer in relation to
more » ... ologic characteristics. We assessed carcinogenic properties of a colon cancer-associated E. coli strain in multiple intestinal neoplasia (Min) mice. Experimental design: Mucosa-associated or internalized E. coli were quantified and characterized from tumors and mucosa of patients with colon cancer and the healthy mucosa of diverticulosis controls. Min mice were inoculated with a colon cancer-associated E. coli strain (11G5). The number of colonic polyps was evaluated at 7 weeks after infection. Results: An increased level of mucosa-associated and internalized E. coli was observed in the tumors compared with normal tissue. A relationship between poor prognostic factors for colon cancer (tumornode-metastasis stage) and colonization of mucosa by E. coli was observed. Pathogenic cyclomodulinpositive E. coli strains were more prevalent on mucosa of patients with stages III/IV than those with stage I colon cancer. Proliferative index and E. coli colonization level of the mucosa distant from the tumor significantly correlated. Min mice infected with the E. coli strain 11G5 displayed a marked increase in the number of visible colonic polyps compared with controls. Conclusion: These findings support that pathogenic E. coli could be a cofactor in pathogenesis of colorectal cancer. Clin Cancer Res; 20(4); 859-67. Ó2013 AACR.
doi:10.1158/1078-0432.ccr-13-1343 pmid:24334760 fatcat:a2k26ymmufcx5lrus2jiifhoj4