Bugs or bacon? How diet and the microbiome influence colorectal cancer risk

2018

Challenge

Obesity, which dramatically raises the risk for colorectal cancer, is a complex biological state influenced by many factors, including diet and the collection of microorganisms in the stomach and intestines, known as the gut microbiome. The contributions to cancer risk from changes in the microbiome caused by an obesity-inducing, high-fat diet versus the effects of the unhealthy diet itself are not currently known.

Advance

IRP researchers led by senior investigator Paul A. Wade, Ph.D., determined that long-term obesity in mice caused DNA in cells lining the colon to be modified in a manner resembling human colorectal cancer. In addition, the researchers showed that those obesity-induced “epigenetic” changes require both an unhealthy diet and a microbiome typical of that found in obese mice.

Impact

This discovery highlights the complex ways the gut microbiome interacts with diet to influence disease risk. Specifically, the findings suggest that changes in the gut microbiome associated with obesity are required for obesity-induced cellular alterations seen in the colon, which may lead to cancer. Consequently, manipulation of the microbiome, in addition to diet alterations, may provide an opportunity for preventive treatments that alter the risk of colorectal cancer in humans who are obese.

Publications

Qin Y, Roberts JD, Grimm SA, Lih FB, Deterding LJ, Li R, Chrysovergis K, Wade PA. (2018). An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression. Genome Biol. Jan 23;19(1):7. doi: 10.1186/s13059-018-1389-1.