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Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown. We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life. We identified patchy bacterial biofilms composed predominately of and Genes for colibactin () and toxin (), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with (expressing colibactin), and enterotoxigenic showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacterial strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.
Cynthia L Sears
Christine Dejea,Payam Fathi,John M Craig,Annemarie Boleij,Rahwa Taddese,Abby L Geis,Xinqun Wu,Christina E DeStefano Shields,Elizabeth M Hechenbleikner,David L Huso,Robert A Anders,Francis M Giardiello,Elizabeth C Wick,Hao Wang,Shaoguang Wu,Drew M Pardoll,Franck Housseau,Cynthia L Sears