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Microbial Bile Acids: A Double-Edged Sword in Colon Cancer Risk
Research conducted at the University of Wisconsin-Madison has shed light on the role of gut microbiota in digestion, particularly how they modify bile acids produced by the liver for fat breakdown. These modifications may influence the risk of developing colon cancer in contrasting ways.
The investigation aimed to deepen the understanding of the complex interactions between gut microbes and human health. Central to this relationship is a specific protein known as the farnesoid X receptor (FXR), which plays a critical role in maintaining gut health through its regulation of bile acids. FXR not only controls bile acid production in the liver but also reacts differently to various bile acids altered by microbial activity.
According to Ting Fu, an assistant professor at UW-Madison’s School of Pharmacy, “Some microbial bile acids support FXR’s function, while others antagonize it.” This research is part of a broader effort to explore FXR as a potential drug target for treating inflammatory bowel disease and colitis, both of which elevate the risk for colon cancer.
The collaborative team, including pharmacy professor Jiaoyang Jiang and Dustin Deming from the UW School of Medicine and Public Health, has identified two specific microbial bile acids that exert opposite effects on FXR. One bile acid enhances the receptor’s function while the other inhibits it, thereby influencing tumor development in the intestines.
Crucially, the study found that the bile acid that supports FXR slows cancer growth, while the one that inhibits it serves as a catalyst for tumor proliferation. These findings were validated in both mouse models of colon cancer and in organoids derived from human patients, underscoring the robustness of the observed effects.
This marks the first documented link between these particular microbial bile acids and their dual roles in colon cancer development and prevention. The findings are published in the Proceedings of the National Academy of Sciences, paving the way for future research into cancer detection and treatment strategies.
As Xingchen Dong, the paper’s lead author and a postdoctoral researcher, notes, “Understanding these complex mechanisms is a significant step toward improving early detection and developing targeted therapies for colorectal cancer. This study not only enhances our knowledge of the relationship between gut microbiota and cancer but also opens new avenues for medical advancements that could potentially benefit millions worldwide.”
Fu emphasizes the intricate nature of the microbial community in our intestines, stating, “It’s fascinating that microbes can modify bile acids in this way and have such a big impact on our body. We have more microbes in our body than our own cells, so when their environment changes due to something like tumor growth, some beneficial microbes attempt to assist in correction, which is highly dependent on their nutritional needs.”
This research received funding from various sources, including University of Wisconsin-Madison startup grants, UWCCC support, and grants from the American Cancer Society and NIH.
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