C. Difficile May Induce Some Colorectal Cancers

Clostridioides difficile (C. difficile), a bacterial species well known for causing diarrheal infections, could also drive colorectal cancer, especially in adults younger than fifty years old, according to data from the Bloomberg-Kimmel Institute for Cancer Immunotherapy and the Johns Hopkins Kimmel Cancer Center.

“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 found that bacterial biofilms were present in more than 50% of people with colorectal cancer, compared to ten to fifteen percent of those without tumors who had biofilms. However, one sample stood out to the researchers when they infected mice with biofilm samples from individuals with colorectal cancer because it significantly increased colorectal tumors in the mice. This slurry caused tumors in eighty-five percent of the mice, compared to most controls, where tumor growth was less than five percent.

In a separate study, the researchers identified a patient without a biofilm that similarly increased colorectal tumors in mice. 

Although several bacterial species have been linked with colorectal cancer — including enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and a specific strain of Escherichia coli, the researchers found that two microbes (B. fragilis and E. coli) were either absent in the tumors of these two patients or did not successfully colonize the mice. These findings suggest that other bacteria were responsible for inducing colorectal cancer.

To determine which bacteria could be causing the tumors, the researchers at John Hopkins performed additional experiments to see if a single bacterial species or a community of bacteria were promoting tumor formation in the mice. They found that while toxigenic C. difficile, the type of C. difficile that causes diarrhea, was absent in samples that did not cause tumors, it was present in those samples that caused tumors in mice. 

On further testing, the researchers added C. difficile to the samples that had not previously caused tumors, and it induced colon cancer in the mice. This suggests that C. difficile alone was sufficient to prompt tumor formation in the animal models.

Another experiment led by Nicholas Markham, M.D., Ph.D., assistant professor of medicine at Vanderbilt University Medical Center, revealed that C. difficile brought about a range of changes within colon cells that made them vulnerable to cancer. According to the study, cells exposed to this bacterium turned on genes that drive cancer and turned off genes that protect against cancer. 

“While this link between C. difficile and colorectal cancer needs to be confirmed in prospective, longitudinal cohorts, developing better strategies and therapeutics to reduce the risk of C. difficile primary infection and recurrence could both spare patients the immediate consequences of severe diarrhea and potentially limit colorectal cancer risk later on,” Julia Drewes, Ph.D., assistant professor of medicine says.

 

Source: John Hopkins Newsroom