Colon cancer: bacterial origin may be involved

Since 1980, several scientific advances have been made in the treatment and prevention of colon cancer. Recent discoveries linking it to a possible bacterial genesis would make it viable to design new methods for improving its detection and prevention.

Possible bacterial genesis may be gateways to improve detection

Since 1980, several scientific advances have been made in the treatment and prevention of colon cancer. Recent discoveries linking it to a possible bacterial genesis would make it viable to design new methods for improving its detection and prevention.

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Bacterial duo believed to be involved in colon cancer development

In a study conducted by a team of cancer immunotherapy researchers at the John Hopkins’ Sidney Kimmel Comprehensive Cancer Center, two bacterial species were found in colon cancer patients in its hereditary form commonly known as familial adenomatous polyposis (FAP). These bacteria have also been found in sporadic forms. Another study conducted on mice highlighted the role of this bacterial colonization in activating colonic oncogenic processes via an immune mechanism.

The mechanism of action elucidated shows a double synergistic action

Bacterial colonization would be at the origin of an invasion of the colonic mucosa, with biofilm formation that is found to induce a series of inflammatory reactions. This chronic colonic inflammation causes damage to cellular DNA. The two bacteria involved were identified through biopsy examination of colonic excisional specimens in patients with FAP. Bacteroides Fragilis (ETBF) acts by producing a toxin that induces an inflammatory reaction in the colonic mucosa. 

The cascade of inflammatory reactions could promote the oncogenic process via IL-17. The latter activates the NF KappaB protein complex resulting in increased recruitment of new immune cells with a role in tumor development. The second bacteria, E. Coli would be at the origin of substance production related to mutagenic action at the cellular DNA level. This double colonization has a simultaneous and synergistic action promoting the process of colonic cancerization. By degrading the mucus layer ETBF promotes the adhesion of PKS + E. Coli to the colon mucosa. Bacterial colonization usually occurs in the childhood period.

New paths for colon cancer prevention

These new insights allow us to consider the development of a new strategy to prevent colon cancer, particularly in people with FAP.

Family adenomatous polyposis is an inherited condition characterized by an increased risk of developing colon cancer. Thanks to this recent discovery, patients with PAF could benefit from a search for biofilms induced by bacteria as part of screening and eradication even before the appearance of polyps. This would avoid the need for surgery in these patients. Screening of people with these bacteria in the colon may also become more common. Finally, and given the bacterial role in the pathogenesis of colonic neoplasia, the use of drugs intended for the treatment and prevention of colon cancer (probiotics, vaccines) could prove to be an interesting option in the future.

1. Christine M. 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. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science, 2018; 359 (6375): 592
2. Liam Chung, Erik Thiele Orberg, Abby L. Geis, June L. Chan, Kai Fu, Christina E. DeStefano Shields, Christine M. Dejea, Payam Fathi, Jie Chen, Benjamin B. Finard, Ada J. Tam, Florencia M. McAllister, Hongni Fan, Xinqun Wu, Sudipto Ganguly, Andriana Lebid, Paul Metz, Sara W. Van Meerbeke, David L. Huso, Elizabeth C. Wick, Drew M. Pardoll, Fengyi Wan, Shaoguang Wu, Cynthia L. Sears, Franck Housseau. Bacteroides
fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. Cell Host & Microbe, 2018

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