While previous studies have linked a high-carbohydrate diet to colorectal cancer, scientists have found it difficult to figure out the exact reason why this is so.

A new study of mice genetically predisposed to colorectal cancer has shown how gut microbes metabolize carbohydrates, which in turn causes intestinal cells to proliferate and form tumors. Importantly, the study also showed how a low-carbohydrate diet significantly reduced tumors in these mice. "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," said Dr. Alberto Martin of the University of Toronto and senior study author, in a press release. The study appears Thursday in Cell.

The ABCs of Carbs

Carbohydrates fall into three categories: starches, sugars, and fiber. Starches include: potatoes, peas, corn, beans, lentils, peas, and grains, including oats, barley, and rice. Sugars include naturally occurring sugars, such as in milk or fruit, and artificial sugars, such as high fructose corn syrup, honey, molasses, and table sugar. Fiber consists of nuts, fruits, and vegetables with edible skins and seeds, and whole grains. Although most of us eat plenty of carbs, they are not essential for survival. In fact, the Recommended Daily Allowance for carbs is zero, and still we continue to eat them. In fact, carbs account for about half of the daily calories consumed by adults on a Western-style diet.

It is crucial, then, for scientists to gain insight into the relationship between carbs and colon tumors. To accomplish this, Martin and his colleagues used mice with APC and MSH2 mutations. Previous scientific studies have shown how mutations in APC, a tumor suppressor gene, and MSH2, which plays a role in repairing DNA damage, are common to colorectal cancers. The team of researchers began their series of experiments by dividing the mice into two groups. Then, they subjected one group to antibiotics, the other to a low-carbohydrate diet.

What did they discover? Both groups of mice showed reduced cell proliferation in addition to a decline in the number of tumors in their small intestines and colons. Both groups also showed reduced levels of those gut microbes that metabolize carbohydrates and produce a fatty acid called butyrate. Extending the experiment, the researchers continued to treat one group of the mice with antibiotics, yet also introduced added butyrate. In this case, cells proliferated and the number of tumors increased in the small intestines of these mice.

Ultimately, the researchers believe these results support the carbohydrate-cancer link and suggest metabolites produced by carb-eating gut microbes drive abnormal cell proliferation and tumor development in mice predisposed to colon cancer. “By providing a direct link between host 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],” wrote the authors in their conclusion

Source:  Belcheva A, Irrazabal T, Robertson SJ, et al. Gut microbial metabolism drives transformation of Msh2-deficient colon epithelial cells. Cell. 2014.