Gut microbes turn carbs into colorectal cancer

July 17, 2014

Colorectal cancer has been linked to carbohydrate-rich western diets, but the underlying mechanisms have been unclear. A study published by Cell Press July 17th in the journal Cell shows 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. 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 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," says senior study author Alberto Martin of the University of Toronto. "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."

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. This type of cancer is also frequently associated with mutations in a called APC as well as the MSH2 gene, which plays a critical role in repairing DNA damage. However, it has been unclear why mutations affecting the DNA repair pathway are much more common in colorectal cancer compared with other cancers. Because gut microbes also contribute to the development of colorectal cancer, Martin and his team suspected that they could interact with diet to explain how the mutations could cause this type of cancer.

To explore this question in the new study, Martin and his collaborators used mice that had APC and MSH2 mutations and thus were predisposed to develop colorectal cancer. Treatment with either antibiotics or a low-carbohydrate diet reduced 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.

Taken together, the findings suggest that carbohydrate-derived metabolites produced by gut microbes drive abnormal cell proliferation and in mice genetically predisposed to colorectal cancer. "By providing a direct link between genetics and , our findings suggest that a reduced in carbohydrates as well as alterations in the intestinal microbial community could be beneficial to those individuals that are genetically predisposed to colorectal ," Martin says.

Explore further: Genetic makeup and diet interact with the microbiome to impact health

More information: Cell, Belcheva et al.: "Gut microbial metabolism drives transformation of Msh2-deficient colon epithelial cells."

Related Stories

Microbes in the gut help determine risk of tumors

November 5, 2013

Transferring the gut microbes from a mouse with colon tumors to germ-free mice makes those mice prone to getting tumors as well, according to the results of a study published in mBio, the online open-access journal of the ...

Gut microbes may be a risk factor for colorectal cancer

December 6, 2013

In one of the largest epidemiological studies of human gut bacteria and colorectal cancer ever conducted, a team of researchers at NYU Langone Medical Center has found a clear association between gut bacteria and colorectal ...

Gut microbes spur development of bowel cancer

March 3, 2014

It is not only genetics that predispose to bowel cancer; microbes living in the gut help drive the development of intestinal tumors, according to new research in mice published in the March issue of The Journal of Experimental ...

Obesity primes the colon for cancer, study finds

April 1, 2014

Obesity, rather than diet, causes changes in the colon that may lead to colorectal cancer, according to a study in mice by the National Institutes of Health. The finding bolsters the recommendation that calorie control and ...

Recommended for you

Combination therapy can prevent cytostatic resistance

November 26, 2015

Researchers at Karolinska Institutet have found a new way of preventing resistance to cytostatics used in the treatment of cancers such as medulloblastoma, the most common form of malignant brain tumour in children. The promising ...

Forecasting the path of breast cancer in a patient

November 23, 2015

USC researchers have developed a mathematical model to forecast metastatic breast cancer survival rates using techniques usually reserved for weather prediction, financial forecasting and surfing the Web.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.