The gut microbiota produces many small molecules, including bile acids, which have been linked to health and disease, but how they affect the body is still not fully understood. Now, researchers have found that certain bile acids produced by gut microbes can interact with specific receptors in the body, influencing immune cells to fight tumors.

The findings, published in Cell, suggest that microbiota-derived metabolites could be used in cancer therapy.

Once thought to only help digest fats, secondary bile acids are now known to act as chemical messengers that influence the body’s immune system and metabolism. However, the exact roles of these molecules and how they work are still unclear—partly because many secondary bile acids are hard to study due to their complex and variable structures.

Researchers led by Wen-Bing Jin at Cornell University in New York set out to explore how bile acids produced by the gut microbiota affect tumor progression and immune responses. 

Androgen signaling

First, the team created a library of 62 known bile acids and analyzed human and mouse stool samples to uncover new versions of these molecules. They found that gut microbes produce compounds with the same building blocks as known bile acids but arranged differently. 

In lab tests, some of these molecules could block the androgen receptor—a protein that responds to male hormones such as testosterone and plays a key role in prostate cell growth and other processes. These bile acids were also able to stop the growth of prostate cancer cells that rely on androgen receptor signaling. 

The researchers identified specific bile acids, including 3-oxo-D4,6-LCA, that are produced by Parabacteroides bacteria and other gut microbes, and that are commonly found in human feces. 

Fighting cancer

Further experiments showed that 3-oxo-D4,6-LCA reduced the growth and spread of tumors in mice, suggesting it could play a role in limiting cancer progression. This bile acid boosted the effectiveness of anti-cancer therapies without side effects on the liver or other organs. It also appeared to promote the differentiation of specific immune cells called CD8+ T cells.

The anti-tumor effects of 3-oxo-D4,6-LCA depended on its interaction with androgen receptors on CD8+ T cells, the researchers found. However, when androgen levels were lowered, the compound’s beneficial effects were reduced.

The findings show that microbiota-derived bile acids influence health and disease by interacting with androgen receptors on immune cells, the authors say. However, they add, further research is needed to better understand the mechanisms behind these effects.