U.S. Department of Health and Human Services

Intestinal Inflammation Works Through Microbes To Raise Cancer Risk

​Researchers have uncovered a surprising interaction between intestinal inlammation and a type of bacteria that promotes colorectal cancer (CRC). Chronic intestinal inlammation is considered a risk factor for CRC, although the process by which it increases risk is unclear. The human intestine is also home to trillions of microbes, which reside near the intestinal cells affected by inlammation and cancer. One research group questioned whether these microbes were innocent bystanders, or if they played a role in the transition from inlammation to cancer within the intestine. First, they sequenced genetic material from bacteria in intestinal and stool samples taken from a mouse model of intestinal inlammation that was genetically programmed to develop colitis (colonic inlammation). They also analyzed samples from control, non-altered mice. The sequencing showed that while the total numbers of intestinal bacteria were similar, the types of microbes found inside the colon differed in mice predisposed to colitis compared to controls. One type of bacteria in particular that was more abundant in the mice with colitis was Escherichia coli (E. coli), which is also more plentiful in the colons of humans with inlammatory bowel disease (IBD) and CRC. When the mice were given a chemical carcinogen, only those predisposed to colitis developed cancer. Next, the researchers inoculated mice raised under germ-free conditions with a single type of intestinal bacteria—either E. coli or another type of bacteria called Enterococcus faecalis (E. faecalis). The colitis-prone mice inoculated with E. coli and given the chemical carcinogen developed an invasive form of colon tumors, while the mice inoculated with E. faecalis and given the carcinogen were less likely to develop invasive tumors. Searching through the E. coli bacterium’s genome, the researchers identiied a gene in some bacterial strains coding for a protein that damages DNA. They found that a strain of E. coli with this toxic gene was more likely to damage DNA in an intestinal cell line compared to another E. coli strain lacking this gene. Likewise, infection of the colitis-prone mice with this toxic strain of E. coli resulted in more numerous and invasive tumors than those in mice infected with the less-toxic strain. The researchers also found this strain of E. coli with the DNA-toxic gene in samples taken from patients with IBD and CRC. This study provides evidence that certain types of intestinal microbes are key players in the complex transformation of colon cells from an inlamed to a cancerous state. Future research will likely focus on other bacterial strains that may contribute to this progression from intestinal inlammation to CRC.

Arthur JC, Perez-Chanona E, Mühlbauer M, et al. Intestinal
inlammation targets cancer-inducing activity of the
microbiota. Science 338: 120-123, 2012.