Gut Microbiome In FAP

The gut microbiome is known to typically be abnormal in patients with sporadic colorectal cancer (CRC).  A study has now shown that individuals with a form of hereditary CRC have bacterial biofilms containing tumorigenic, cancer-promoting bacterial strains, and exhibit cancer-promoting gene expression due to this bacterial colonization.  Mouse models of CRC exhibit accelerated tumor development when colonized by these strains.  These important findings underscore the importance of the gut bacteria and suggests targets for therapeutic intervention. Abstract:

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 Escherichia coli and Bacteroides fragilis Genes for colibactin (clbB) and Bacteroides fragilis toxin (bft), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with E. coli (expressing colibactin), and enterotoxigenic B. fragilis 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.