Microorganisms residing in our intestines play a crucial role in breaking down food by transforming the bile acids produced by our livers, which are essential for fat digestion. Recent research suggests that two of these modified bile acids can influence our risk of colon cancer in opposing ways. This connection was revealed as scientists at the University of Wisconsin-Madison aimed to enhance our understanding of how gut microbes interact with our bodies.
Microorganisms residing in our intestines play a crucial role in breaking down food by transforming the bile acids produced by our livers, which are essential for fat digestion. Recent research suggests that two of these modified bile acids can influence our risk of colon cancer in opposing ways.
The relationship between these bile acids and the risk of colon cancer was recently discovered as researchers from the University of Wisconsin-Madison explored the interactions between gut microbes and our health.
A key player in this relationship is a specific protein known as the farnesoid X receptor (FXR), which is vital for a healthy gut and has a close connection with bile acids. FXR regulates the formation of bile acids in the liver and reacts differently to various bile acids altered by microbes.
“Some microbial bile acids enhance FXR’s function while others counteract it,” explains Ting Fu, an assistant professor at the UW-Madison School of Pharmacy. Fu and her team previously recognized FXR as a potential target for drug development aimed at treating inflammatory bowel disease and colitis, which heightens the risk of colon cancer.
Now, a research group headed by Fu, along with pharmacy professor Jiaoyang Jiang and associate professor Dustin Deming from the UW School of Medicine and Public Health, has pinpointed two microbial bile acids that have opposing effects on FXR during tumor progression in the intestines; one enhances its function while the other inhibits it.
Crucially, the impact of these bile acids on FXR is linked to tumor growth, but with an interesting twist. The bile acid that boosts FXR’s function hinders cancer growth, whereas the one that inhibits FXR promotes tumor development.
These findings were consistent across various colon cancer mouse models studied, as well as organoids—tiny lab-grown replicas of human organs—derived from individuals with colon cancer.
For the first time, this research has associated these specific microbial bile acids with either the advancement or prevention of colorectal cancer. The findings were published in the journal Proceedings of the National Academy of Sciences. This research opens pathways for exploring innovative methods for cancer detection and new treatment options.
“Deciphering these intricate processes is a crucial milestone in enhancing early detection and developing targeted treatments for colorectal cancer,” states Xingchen Dong, a postdoctoral researcher at UW’s pharmacy school and the lead author of the study. “This research not only deepens our understanding of the complex relationship between gut microbiota and cancer but also paves the way for medical developments that could benefit countless individuals globally.”
Fu emphasizes that the contrasting roles of bile acids in the development of intestinal tumors highlight the complexity of our gut microbial community.
“It’s fascinating that microbes can alter bile acids in such ways and have such significant effects on our health,” she remarked. “We have more microbes in our bodies than human cells, so when changes occur in their environment, like tumor growth, some beneficial microbes attempt to help. However, this depends entirely on their nutritional needs.”
This research was funded by various grants from the University of Wisconsin-Madison, including startup grants (AAI3795, AAI3894), UWCCC startup support (AAI5122), and others from organizations such as the Wisconsin Alumni Research Foundation and the American Cancer Society.
