Linking Inflammation to Bacteria and Cancer

e live with trillions of microbes in our gut, a rich community of bacteria and other microorganisms that metabolize foods and support our health. A new animal study published in Science now suggests that gut inflammation alters this microbial community – our microbiota – fostering the growth of a toxic form of bacteria that may then cause colorectal cancer. The research also linked this toxic bacterium – a form of E. coli – to human cancer: People with colorectal cancer had relatively higher proportions of this E. coli strain than healthy people. The study, partially supported by AICR, suggests a novel and complex interaction in which our microbiota and an inflammatory microenvironment act in concert with one another to promote colon cancer. The work identified the toxic bacterium as a form of E. coli carrying genes called pks (polyketide synthase). “It’s long been a dogma in cancer research that inflammation promotes cancer, but the mechanism by which inflammation increases colon cancer risk isn’t known,” said James C. Fleet, PhD, a professor in food and nutrition at Purdue University and an expert on colon cancer prevention who was not involved in this study. “This work is so important because it provides a unique perspective.... It says we have to consider the impact of the gut microbiome on cancer risk and it suggests that we could reduce colon cancer risk if we could reduce the number of microbes in the gut that have the pks gene.” Aggressive and Pathogenic Researchers already knew that people with inflammatory bowel diseases are at increased risk of developing colorectal cancer. And there are microbes recognized to cause cancer, such as the bacterium Helicobacter pylori for stomach cancer. But there are numerous strains of harmless E. coli and many are living in our gut. microbiota with far fewer kinds of microbes and a 100-fold increase of one form of E. coli. They identified this strain of E. coli as an aggressive form already linked to damaging DNA. Later they found it carried pks genes and produces a toxin called colibactin. When the researchers placed E. coli with and without pks in mice prone to inflammation, the E. coli pks promoted tumor formation. The E. coli without the pks gene decreased the ability of tumors to invade and multiply. Then the scientists looked at tissues from 80 people. One group was from colon cancer patients and another group of people had inflammatory bowel disease, conditions that involve inflammation. The third group was the comparison, without inflammation or cancer. Two-thirds of the colorectal cancer patients and about a third of the patients with inflammation had E. coli that carried the pks gene. Only one-fifth of the comparison group had the pks bacteria. Still, having this E. coli pks, by itself, was not enough to promote cancer in mice. In the absence of inflammation, mice given the bacteria did not develop inflammation or cancer. Inflammation sets up the perfect environment for E. coli pks to cause cancer, says Jobin. It shifts the gut’s microbial strains and also allows the toxic bacteria to adhere to the epithelial cells that line our colon and where colon cancer begins, the work purports. “You may have this E. coli and it may not come into close contact with your epithelium because we have a lot of defense mechanisms in place that keep them from invading,” says Jobin. “These bugs are just sitting there, being quiet until an opportunity comes.... The inflammation allows them to expand, they have the opportunity and the numbers to then interact with the host – everything together is like the perfect storm.” “These bugs are just sitting there, being quiet until an opportunity comes.”