Carbs and gut microbes fuel colon cancer

Sugar-loving bacteria support the emergence of tumors in mice

COLON CARBS  In mouse colons, sugar-loving gut microbes encourage mutations in DNA (blue), which elevate cancer-related proteins (green), possibly explaining why Western nations experience more colon cancer.

Antoaneta Belcheva and Alberto Martin

Westerners’ carb-rich diets have long been linked to high levels of cancer, and scientists have begun to work out why. In an experiment with mice, gut bacteria bridged the gap, explaining why sugar-heavy diets can cause cancer, researchers report in the July 17 Cell.

Colorectal cancer ranks third on the list of deadliest cancers, and the disease hits developed countries harder than developing ones. Nearly one of every 15 people in Western nations will suffer from the condition, and doctors suspect that carbohydrate-laden diets contribute to the problem.

In country after country where people have switched to Western-style diets heavy in refined sugars such as high fructose corn syrup, the incidence of colorectal cancer has increased, says geneticist Scott Bultman of the University of North Carolina, Chapel Hill, who was not involved in the study. Until now, the underlying connection between food and colon cancer has been cloudy. “This study gives a good mechanism for how diet is tied to colon cancer,” Bultman says.

To probe the link between colon tumors and gut microbes, the researchers treated mice engineered to be prone to colon cancer with antibiotics. By reducing intestinal bacteria, the drugs hindered malignant lumps of cells called polyps from growing in the lining of the colon and small intestines. The team then noticed that feeding the rodents a diet low in sugar and starch also reduced the growth of polyps.

The mice had two gene mutations often linked to colon cancer in people, one of which derails a cell’s ability to fix errors that arise during DNA replication, known as the mismatch DNA repair system.

A mismatch repair deficiency causes cells in the lining of the colon to divide quickly, explains study leader Alberto Martin, an immunologist at the University of Toronto. Bacteria and carbs speed the process, he says, damaging the genome and leading to tumor growth.

The researchers surmised that when microbes feast on carbohydrates, the bacteria must produce a chemical that pushes colon cells lacking the ability to repair DNA mismatches toward uncontrollably multiplying into tumors. To find that chemical, they looked to the colon contents of mice that ate low-carb diets or had received antibiotics. Those mice, compared with mice on regular diets, had lower levels of a fatty acid called butyrate, one of the byproducts of microbes’ fermentation of carbohydrates.

The researchers then fed mice butyrate-enriched supplements. Those mice had more tumor polyps, suggesting that the path from Western diets to colon cancer relies on this bacterially produced chemical.

In people, mismatch repair mutations are present in one out of five cases of noninherited colon cancer. If the mouse experiments mimic human cancers, then shunning high-carbohydrate, Western diets could allay or prevent the disease for many people, says Bultman. “Following a well-balanced diet, with fewer refined sugars and more fiber, is good for the microbiome and likely has an effect on cancer predisposition.”

Editor’s Note: This article was updated August 7, 2014, to clarify that antibiotics reduced intestinal bacteria in the mice.

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