C. difficile drives some colorectal cancers, study suggests: Common infection could be one driver of colorectal cancer rise in younger adults

Data collected by researchers at the Johns Hopkins Kimmel Cancer Center and the Bloomberg~Kimmel Institute for Cancer Immunotherapy suggest that Clostridioides difficile, or C. diff, a bacterial species well known for causing serious diarrheal infections, may also drive colorectal cancer.

The findings were published June 9 in Cancer Discovery, and may expose another troublesome role for this microbe, which causes approximately 500,000 infections a year in the U.S. — many of which prove incredibly difficult to clear.

“The uptick of individuals under age 50 being diagnosed with colorectal cancer in recent years has been shocking. We found that this bacterium appears to be a very unexpected contributor to colon malignancy, the process by which normal cells become cancer,” says Cynthia Sears, M.D., Bloomberg~Kimmel Professor of Cancer Immunotherapy and professor of medicine at the Johns Hopkins University School of Medicine.

Several years ago, researchers in the Sears Lab discovered that more than half of patients with colorectal cancer had bacterial biofilms — dense collections of bacteria on the colon surface — whereas 10% to 15% of healthy patients without tumors displayed biofilms. However, when the researchers infected mice with biofilm samples derived from individual people with colorectal cancer, one sample caught their attention because it markedly increased colorectal tumors in the mice. Whereas in most controls, less than 5% develop tumors, this slurry induced tumors in 85% of mice.

In additional work, the team identified a patient sample without a biofilm that similarly increased colorectal tumors in the mice. Although several bacterial species have been linked with colorectal cancer — including enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum and a specific strain of Escherichia coli — these microbes were either absent in the tumors of these two patients (B. fragilis and E. coli) or did not successfully colonize the mice (F. nucleatum), suggesting that other bacteria were responsible for promoting the colorectal cancer cascade.

To determine which bacteria may be causing tumors in the mice, Sears, along with study co-authors Julia Drewes, Ph.D., assistant professor of medicine, Jie (Angela) Chen, Ph.D., Jada Domingue, Ph.D., of Johns Hopkins, and colleagues performed additional experiments to see if a single bacterial species or a community of bacteria were promoting tumor formation in the mice. They noted that toxigenic C. difficile, the type of C. difficile that causes diarrhea, was absent in the samples that did not cause tumors, but was present in the samples that caused tumors in mice. When the researchers added this bacterium to the samples that originally did not cause tumors, it induced colon tumors in the mice. Further testing showed that C. difficile alone was sufficient to prompt tumor formation in the animal models.

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