Gut Bacteria May Reveal How a Western Diet Fuels Colon Cancer - ScienceAlert

Add ScienceAlert on Google (puhimec/iStock/Getty Images Plus) Colorectal cancer is one of the most common cancers worldwide, and what we eat can significantly influence our risk of developing it. Western-style diets, typically high in fat and meat but low in fiber, have long been linked to a higher risk of the disease. But exactly how this pattern of eating may encourage tumors to develop has remained unclear. A new study published in the journal Gut may have taken us a step closer to understanding the exact mechanism at play. The study suggests that certain gut bacteria in the depths of our bowels, sustained by Western-style diets, may produce a substance that promotes tumor growth. An international research team led by German institutions combined experiments in genetically modified pigs, mice, and lab-grown human colon tissue with an analysis of microbial data from thousands of people with and without colorectal cancer. Their findings point to deoxycholic acid (DCA), a substance produced when particular gut bacteria chemically transform bile acids made by the liver. Bile acids play an essential role in digestion. Produced from cholesterol in the liver and released into the small intestine, they help the body break down and absorb fats. Most bile acids are later reabsorbed and returned to the liver, but a small proportion reaches the colon. There, bacteria capable of a process called 7-alpha-dehydroxylation can convert primary bile acids into secondary ones, including DCA. Higher concentrations of DCA and the bacteria that produce it have previously been observed in people with colorectal cancer. A 2024 study published in Immunity also found that DCA weakened the activity of immune cells that help attack tumors and promoted colorectal tumor growth in mice. However, earlier research had not established whether bacterial DCA production directly connected a Western-style diet with colorectal cancer development. The gut microbiome is a vast community of bacteria and other microbes that reside in our intestines; while relatively easy to sample, it's a complex ecosystem that's difficult to untangle. To investigate this more directly, the researchers first examined genetically modified pigs predisposed to developing polyps in the colon. When the pigs were fed a Western-style diet, intestinal tumor development worsened. This was accompanied by higher DCA levels in their feces and increased proliferation of the epithelial cells lining the colon. The researchers then treated some pigs with cholestyramine, a drug that binds bile acids in the digestive tract so they can be removed from the body. With those bile acids removed, there was less excessive cell proliferation in the colon, strengthening the suspected connection between bile acids and tumor development. The team next turned to germ-free mice, whose intestinal microbial communities could be precisely controlled. Adding DCA-producing bacteria, including Clostridium scindens and Extibacter muris, to defined communities of gut microbes led to DCA production and increased the number of colon tumors in two different mouse models of colorectal cancer. In another experiment, the researchers genetically modified the bacterium Faecalicatena contorta so it could no longer perform the reaction required to produce DCA. Mice colonized with the genetically altered bacteria developed fewer colon tumors than those carrying the unmodified, DCA-producing strain. The modified bacteria also caused less epithelial cell proliferation in human colon organoids – miniature, simplified versions of colon tissue grown in the laboratory. To examine whether the same bacterial machinery was associated with colorectal cancer in people, the researchers analyzed microbial DNA from stool samples collected across several human cohorts. These data comprised 1,034 individuals with colorectal cancer and 1,108 without. Genes involved in DCA production, particularly those associated with C. scindens and closely related bacteria, were found more frequently in people with colorectal cancer than in those without the disease. Together, the findings support a possible chain of events: A high-fat Western diet alters bile acid metabolism by promoting certain gut bacteria that convert primary bile acids into DCA, and DCA stimulates abnormal cell proliferation, creating conditions that may support tumor growth. "Our results show how much a Western high-fat diet and the associated changes in the gut microbiome can affect human gut health," microbiologist Sören Ocvirk, of the German Institute of Human Nutrition Potsdam-Rehbruecke, said in a press release. The experiments providing evidence of causality were conducted in animal models already predisposed to the disease. The human component was observational, meaning it could identify an association but not prove that bacterial DCA production caused cancer in those participants. The study also does not demonstrate that cholestyramine can prevent or treat colorectal cancer in people. Clinical trials would be needed before bile acid-binding drugs, microbiome tests, or treatments targeting particular bacterial pathways could be used for cancer prevention. Related: One Diet Helped Aging Mice Lose Fat While Preserving Muscle Still, the research provides a possible biological explanation for an association scientists have observed for years and may eventually help identify people whose gut microbiomes make them especially vulnerable to unhealthy diets. For now, the findings reinforce existing dietary advice rather than establishing a new treatment: Diets rich in fiber, fruit, vegetables, and whole grains, and lower in processed and red meat, are associated with a reduced risk of colorectal cancer. This article was fact-checked by Fiona MacDonald and edited by Clare Watson. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.