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The article focuses on genotoxic gut bacteria which damage or mutate DNA are critical drivers of colorectal cancer (CRC) pathogenesis. Topics include considered the notable increase in early-onset CRC incidence highlights the urgency to discover responsible exogenous factors that are amenable to therapeutic intervention.

The article discusses gut microbiota and how it acts as a critical determinant for immunotherapy responses. It cites a research by L. F. Mager published in this issue, which reveals how inosine produced by specific gut bacteria improves immune checkpoint inhibitor (ICI) efficacy in numerous mouse models. It mentions the need to understand the biosynthetic metabolite redundancy among bacterial species.

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. [ABSTRACT FROM AUTHOR]