​​Dr Byndloss on the Relationship Between Gut Health and the Risk of Developing CRC

Mariana X. Byndloss, DVM, PhD, assistant professor of pathology, microbiology and immunology, Vanderbilt University Medical Center, discusses the relationship between the gut microbiome and the risk of developing cancers such as colorectal cancer (CRC).

An increasing body of evidence has elucidated a potential role for gut microbiomes in the development and successful treatment of certain cancers, Byndloss begins. The interaction between diet and the health of commensal gut bacteria is one particular way that gut health may influence cancer susceptibility both in and outside of the gastrointestinal tract, Byndloss states.

High-fat diets have been shown to drive tumorigenesis by inducing microbial dysbiosis and metabolic dysregulation, altering the level of metabolites, and causing gut barrier dysfunction in colonic carcinogenic mouse models. Other potential functional contributions to cancer etiology include the ability of gut bacteria to harvest inaccessible nutrients from the diet such as fiber, their ability to prevent the metabolism of certain cancer treatments, and their influence on immune system activation and systemic inflammation.

The health of gut microbiota has been linked to the development of CRC, Byndloss continues. Proinflammatory microbes can increase inflammatory tone in the intestines, which increases risk, she says. Furthermore, many microbes produce metabolites that directly promote carcinogenesis. For example, some strains of E.Coli carry the pathogenicity island pks, which encodes for a gene known as colibactin, Byndloss states. Once synthesized, colibactin causes double-stranded DNA breakage and can lead to cell cycle arrest for eukaryotic cells, and apoptosis in immune cells, Byndloss explains. The mutational signature induced by this genotoxin has also been implicated in the development of CRC, Byndloss adds.

Other obligate anaerobic, Gram-negative microbes such as Fusobacterium and Bacteriodes fragilis also have shown direct carcinogenic potential because of their metabolites on epithelial cells in the intestines, Byndloss concludes.