Western Diet, Gut Bacteria, and Colorectal Cancer: New Mechanistic Insight

An international research team led by German institutions published a study in *Gut* that investigates how a high-fat Western-style diet may promote colorectal cancer. The investigators combined experiments in genetically modified pigs, germ-free mice, laboratory-grown human colon organoids, and an analysis of stool-derived microbial DNA from more than two thousand people. Their central finding is that dietary patterns that increase bile-acid concentrations foster gut bacteria that convert primary bile acids into the secondary bile acid deoxycholic acid (DCA), which in turn stimulates abnormal epithelial cell proliferation—a key step in tumor development.

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In pigs predisposed to colon polyps, feeding a Western-style diet accelerated tumor growth, coinciding with elevated fecal DCA levels. Treatment with cholestyramine, a bile-acid-binding drug, reduced both DCA and excessive cell proliferation, strengthening the link between bile acids and tumorigenesis. In germ-free mice, introduction of DCA-producing species such as *Clostridium scindens* and *Extibacter muris* increased tumor numbers in two colorectal-cancer mouse models. Conversely, mice colonized with a genetically engineered strain of *Faecalicatena contorta* that cannot produce DCA developed fewer tumors and showed reduced epithelial proliferation in human colon organoids.

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The researchers examined stool samples from 1,034 individuals diagnosed with colorectal cancer and 1,108 cancer-free controls. Genes encoding the enzymatic pathway for DCA production—particularly those linked to *C. scindens* and related bacteria—were more prevalent in the cancer cohort, suggesting an association between DCA-producing microbes and disease in humans.

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Microbiologist Sören Ocvirk of the German Institute of Human Nutrition Potsdam-Rehbrücke explained that the results illustrate how a high-fat Western diet can reshape the gut microbiome to increase DCA levels, thereby creating a pro-tumor environment. He emphasized that the animal experiments demonstrate causality, whereas the human data remain observational; consequently, the study does not prove that DCA production directly causes cancer in people, nor that cholestyramine would be an effective preventive therapy without further clinical trials.

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The findings provide a biological rationale for longstanding dietary recommendations that associate high fiber, fruit, vegetable, and whole-grain intake with lower colorectal-cancer risk, while limiting processed and red meat. Although the research points toward potential future interventions—such as bile-acid-binding agents or microbiome-targeted therapies—current evidence supports reinforcing existing dietary guidance rather than adopting new clinical treatments.

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