More Findings on Risks From Carb-Heavy Diet in Hereditary Colorectal Cancer

Researchers now have a better idea of how a mismatch in the DNA repair protein can lead to the development of colorectal cancer.

In a new study, published this month in Cell, researchers have shown that gut microbes metabolize carbohydrates in the diet, causing intestinal cells to proliferate and form tumors in mice that are genetically predisposed to colorectal cancer.

Researchers also found that treatment with antibiotics or a low-carbohydrate diet significantly reduced tumors in these mice, suggesting that these easy interventions could prevent a common type of colorectal cancer in humans.

"Because hereditary colorectal cancer is associated with aggressive and rapid tumor development, it is critical to understand how major environmental factors such as microbes and diet interact with genetic factors to potentially affect disease progression," senior study author Alberto Martin, PhD, of the University of Toronto, said in a press release. "Our study provides novel insights into this question by showing that gut bacteria interact with a carbohydrate-rich diet to stimulate a prevalent type of hereditary colon cancer."

Colorectal cancer is frequently associated with mutations in a tumor suppressor gene called APC as well as the MSH2 gene, which plays a critical role in repairing DNA damage.

Carbohydrates account for about half of the daily caloric intake of adults on a western-style diet, and previous studies have linked carbohydrate-rich diets to colorectal cancer in humans.

To further understand the interaction between the MSH2 gene and the development of colorectal cancer, Martin and his collaborators used mice that had APC and MSH2 mutations.

Treatment with either antibiotics or a low-carbohydrate diet reduced cell proliferation as well as the number of tumors in the small intestines and colons of these mice. These two treatments also reduced levels of certain gut microbes that metabolize carbohydrates to produce a fatty acid called butyrate. When the researchers increased butyrate levels in the antibiotic-treated mice, cell proliferation and the number of tumors increased in the small intestines.

"By providing a direct link between genetics and gut microbes, our findings suggest that a diet reduced in carbohydrates as well as alterations in the intestinal microbial community could be beneficial to those individuals that are genetically predisposed to colorectal cancer," Martin says.