Colorectal cancer rates are rising, and mortality rates for this disease are relatively high; in 2022 alone about 1.9 million people were newly diagnosed, and around 900,000 people died from the disease. A variety of factors including genetics, diet, and the gut microbiome can affect the risk of developing colorectal cancer, which has been linked to high-fat and high-sugar, Western-style diets. These diets can encourage gut microbes to produce secondary bile acids, and scientists have now shown that some of these secondary bile acids may lead to colorectal cancer. The findings, which were reported in Gut, could help scientists and clinicians reduce colorectal cancer risk through dietary changes.
When people eat a lot of fat, microbes in the gut known as 7αDH-positive bacteria can use that fat to make secondary bile acids; these microbes are capable of 7-alpha-dehydroxylation, leading to deoxycholic acid (DCA) production. High levels of DCA are linked to a higher risk of colorectal cancer.
In this work, researchers used a pig model that gets colon polyps. They showed that Western-style diets promote tumor growth in the intestines of these pigs. The growth of intestinal cells was boosted by high levels of bile acids, especially DCA, noted the researchers. When a drug called cholestyramine was used to remove bile acids, tumor growth was reduced.
There was also rapid growth of intestinal epithelial cells in a mouse model that carried only DCA-generating, 7αDH-positive bacteria in their guts.
Additional work showed that colorectal cancer patients carried higher levels of 7αDH-positive bacteria in their guts than unaffected individuals.
It may be possible to identify people who are at risk of colorectal cancer by assessing their gut microbes, or using dietary changes to reduce the risk of the disease, the study suggested.
"Our results show how much a Western high-fat diet and the associated changes in the gut microbiome can affect human gut health in the long term,” said senior study author Dr. Sören Ocvirk, Head of Gnotobiology at the German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE).
More research will be needed to understand exactly how secondary bile acids can raise the risk of of cancer, but this study shows that it may be possible to lower an individual’s risk of some types of cancer with dietary interventions.
Sources: Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke, Gut
