Our digestive system is an active center filled with trillions of microorganisms that engage with our bodies to promote our well-being. A recent study delves into an intriguing detail of this relationship: the collaboration between gut bacteria and our body in controlling bile acids, which are vital substances that manage digestion, cholesterol levels, and fat metabolism.
“Bile acids are generated in the liver and assist in fat digestion,” said Frank Schroeder, a professor at the Boyce Thompson Institute and a lead author of the study. “However, it’s become evident that they serve more purposes than just aiding digestion; they function as signaling molecules that regulate cholesterol levels, fat metabolism, and additional processes. They achieve this by binding to a receptor known as FXR, which operates like a traffic signal, governing cholesterol metabolism and bile acid production to prevent excessive accumulation.”
This is where microbiota play a role: gut bacteria can alter bile acids, significantly changing their function. These bacteria can transform bile acids into variants that effectively activate FXR, prompting the body to decrease bile production and adjust various aspects of fat metabolism. Researchers have long pondered how the body counters this microbial influence on metabolism.
In a recently published study in Nature, Schroeder and his team uncovered a clever mechanism that the body employs to keep microbial effects in line, using mice as study subjects. They discovered that inside the intestines, the body further modifies the bacterial bile acids into a new group of derivatives called BA-MCYs, through the action of an enzyme named VNN1. Unlike the forms produced by gut bacteria, these BA-MCYs serve as FXR antagonists — essentially turning off FXR’s activity. This encourages the production of bile instead of restricting it.
“This balancing act is vital,” Schroeder noted. “When gut bacteria generate high levels of bile acids that intensely activate FXR, the body retaliates by producing BA-MCYs, ensuring that the bile acid system remains finely tuned. This interaction illustrates the dynamic give-and-take relationship between gut microbes and the host body.” Notably, BA-MCYs were also found in human blood samples, suggesting that this mechanism also functions in humans.
The implications of these findings for health and illness are promising. The researchers found that increasing BA-MCY levels in mice helped mitigate fat buildup in the liver, pointing to a possible treatment for conditions such as fatty liver disease or elevated cholesterol. Additionally, dietary changes, like increasing fiber consumption, boosted BA-MCY production, indicating the influence of diet on managing this system.
“Our study shows there is an ongoing conversation between gut microbes and the body that is crucial for regulating bile acid production,” stated co-corresponding author Dr. David Artis, who leads the Jill Roberts Institute for Research in Inflammatory Bowel Disease and the Friedman Center for Nutrition and Inflammation, as well as being the Michael Kors Professor in Immunology at Weill Cornell Medicine.
While this discovery illuminates a previously overlooked aspect of gut chemistry, many questions persist. How do diet and lifestyle affect BA-MCY levels? Might these compounds assist in managing conditions like diabetes or metabolic syndrome? Future studies could lead to tailored interventions that leverage this host-microbe collaboration to enhance health.
“Our paper serves as a guide to utilizing untargeted metabolomics and chemistry to gain insights into how the interaction between gut microbiota and the body influences various diseases,” Dr. Artis remarked.
The research showcases the collaborative effort between our bodies and gut bacteria within an interconnected framework aimed at sustaining metabolic balance. It serves as a reminder that we are not isolated entities — we are ecosystems, intricately linked to the microbial world inside us.
