Study Finds High-Fat Diets Alter Gut Bacteria and Increase Colorectal Cancer Risk

The escalating prevalence of colorectal cancer among individuals under 50 years old has been attributed to factors like obesity and high-fat diets. A recent study by researchers at the Salk Institute and UC San Diego delves into the connection between high-fat diets, gut bacteria, and bile acids. The findings, published in Cell Reports, reveal that high-fat diets can lead to changes in gut bacteria, which in turn modify bile acids, ultimately predisposing mice to colorectal cancer.

The research discovered heightened levels of specific gut bacteria in mice subjected to high-fat diets. These bacteria were shown to reshape the bile acid composition, leading to inflammation and influencing the rate at which intestinal stem cells replenish. Bile acids, produced by the liver and aiding digestion and nutrient absorption, were found to be affected by these changes.

Co-senior author and Professor Ronald Evans, emphasized that "alterations in the gut microbial population can create problems that lead to cancer." In a previous study, Evans and his team demonstrated how high-fat diets raised overall bile acid levels, which subsequently deactivated a crucial protein in the gut, the Farnesoid X receptor (FXR), and contributed to a higher cancer prevalence.

However, understanding the role of the gut microbiome and bile acids remained incomplete. In the current study, the team examined the microbiomes and metabolomes of animals on high-fat diets, particularly focusing on mice with a genetic predisposition to colorectal tumors.

The study found that high-fat diets resulted in a less diverse collection of bile acids in the gut, with specific bile acids altered by gut bacteria. These modified bile acids influenced the proliferation of intestinal stem cells, which, when mutated, can promote cancer growth. Additionally, the gut microbiomes of mice on high-fat diets were less diverse and included different bacteria compared to those on regular diets.

The study highlights the profound impact of high-fat diets on microbiomes and modified bile acids, even surpassing the influence of genetic mutations associated with cancer susceptibility. The researchers suggest that high-fat diets reshape the microbiome, encouraging the growth of specific bacteria that lead to modified bile acid levels, thereby creating an inflammatory environment conducive to cancer.

By deciphering the mechanism connecting high-fat diets to increased cancer risk, the researchers aim to pave the way for preventive and therapeutic interventions. Future investigations will explore how quickly the microbiome and bile acids change once a high-fat diet is initiated, as well as strategies to reverse cancer-associated effects by targeting FXR, a protein associated with bile acid modifications.