Colorectal cancer is one of the most common cancers worldwide, and growing evidence suggests diet plays a major role in determining who develops the disease. Western-style diets, typically high in fat and red or processed meat but low in fiber, have long been associated with an increased risk of colorectal cancer. Until now, however, the biological mechanism linking diet to tumor development has remained unclear.
A new study published in the medical journal Gut provides one of the strongest explanations to date. An international team of researchers found that a Western diet appears to promote the growth of specific gut bacteria that produce a bile acid byproduct capable of encouraging tumor formation. The findings combine evidence from animal models, laboratory-grown human tissue and thousands of human stool samples.
How gut microbes turn diet into cancer risk
The study focused on deoxycholic acid (DCA), a secondary bile acid produced when certain gut bacteria chemically modify primary bile acids made by the liver. Primary bile acids are essential for digesting dietary fats and are largely reabsorbed in the small intestine before returning to the liver. A small portion, however, reaches the colon, where gut microbes can convert them into secondary bile acids.
In the colon, bacteria capable of performing a reaction known as 7-alpha-dehydroxylation transform primary bile acids into secondary forms, including DCA. Previous studies have repeatedly found elevated levels of DCA and DCA-producing bacteria in people with colorectal cancer, while laboratory research has shown that DCA can damage DNA and alter immune responses within the gut. What remained uncertain was whether dietary changes could directly drive these microbial alterations and promote tumor growth in living organisms.
Evidence from pigs, mice and human organoids
To investigate this process, researchers first studied genetically modified pigs that are naturally prone to developing intestinal polyps. Animals fed a Western-style high-fat diet developed more intestinal tumors than pigs receiving a standard diet. They also had higher concentrations of DCA in their feces and showed increased cell proliferation in the lining of the colon.
The researchers then treated some pigs with cholestyramine, a medication that binds bile acids in the intestine and prevents them from being reabsorbed. Animals receiving cholestyramine showed reduced abnormal cell proliferation in the colon, providing additional evidence that bile acids contribute to the early stages of tumor development. Although this does not demonstrate that the drug prevents colorectal cancer in humans, it strengthens the hypothesis that bile acid metabolism influences cancer risk.
The team next turned to germ-free mice, which lack their own gut microbiome and allow researchers to introduce carefully controlled bacterial communities. When scientists introduced DCA-producing bacteria—including Clostridium scindens and Extibacter muris—the animals produced measurable amounts of DCA and developed more colon tumors in two separate mouse models genetically predisposed to colorectal cancer.
To determine whether DCA itself was responsible, the researchers genetically modified another gut bacterium, Faecalicatena contorta, preventing it from producing DCA. Mice colonized with this modified strain developed fewer tumors than mice carrying the normal DCA-producing bacteria. Similar results were observed in laboratory-grown human colon organoids, where the modified bacteria stimulated significantly less cell proliferation, suggesting comparable mechanisms may operate in human tissue.
The same pattern appeared in human populations
To examine whether these findings extended beyond animal models, the researchers analyzed stool samples collected from multiple international human cohorts. They examined microbial DNA from 1,034 individuals with colorectal cancer and 1,108 healthy controls, searching for bacterial genes involved in DCA production.
Genes responsible for the critical 7-alpha-dehydroxylation pathway were significantly more common in samples from individuals with colorectal cancer. In particular, genetic signatures associated with Clostridium scindens and related bacteria appeared more frequently in cancer patients than in healthy participants.
Although these findings cannot establish cause and effect, they reveal a remarkably consistent association between DCA-producing microbial pathways and colorectal cancer.
Taken together, the results support a plausible biological sequence. A Western-style high-fat diet increases bile acid levels within the intestine, creating favorable conditions for bacteria capable of converting these bile acids into DCA. Elevated DCA then promotes excessive cell growth and other biological changes that may increase the likelihood of tumor formation and progression.
According to study co-author Sören Ocvirk of the German Institute of Human Nutrition, the findings demonstrate how strongly diet and the gut microbiome interact to influence colorectal health.
Implications for prevention and future research
The researchers emphasize that much of the direct mechanistic evidence comes from animal models genetically predisposed to colorectal cancer, while the human data remain observational. As a result, the study cannot prove that DCA production directly caused cancer in the human participants. Carefully designed clinical trials will be necessary to determine whether reducing DCA levels or targeting DCA-producing bacteria can lower colorectal cancer risk.
The study also does not establish cholestyramine or other bile acid-binding medications as proven preventive treatments. Their long-term effects on the gut microbiome, nutrient absorption and overall health would require thorough investigation before such approaches could be recommended.
Nevertheless, the findings may help guide future research into microbiome-based screening tools and targeted therapies designed to reduce DCA production in people at elevated risk.
For now, the study reinforces existing public health recommendations. Diets rich in fiber, fruits, vegetables and whole grains, while limiting processed and red meat, consistently remain associated with a lower risk of colorectal cancer. Fiber may be particularly beneficial because it supports a more diverse gut microbiome, reduces intestinal inflammation and helps dilute or accelerate the elimination of potentially harmful bile acid byproducts.
As colorectal cancer continues to rise in countries adopting increasingly Westernized diets, understanding the biological links between food, gut microbes and tumor development is becoming increasingly important. This research suggests that modifying the gut microbiome through diet—and potentially through future targeted therapies—could eventually become part of personalized colorectal cancer prevention.
