A new preclinical study led by researchers from Weill Cornell Medicine and the Boyce Thompson Institute at Cornell University reveals how beneficial gut microbes and the body work in tandem to regulate fat metabolism and cholesterol levels. The study highlights the complex relationship between the human body and gut microbiota, emphasizing the role of gut bacteria in fine-tuning bile acid production, which is essential for digesting fat and regulating cholesterol.
The gut microbiota, a community of beneficial microbes living in the human digestive system, plays a crucial role in food digestion and the absorption of vital nutrients. This relationship, honed over millennia of co-evolution, involves the production of bioactive molecules, one of the most significant being bile acids. These acids are produced in the liver from cholesterol and transported to the intestine, where they aid in fat digestion and nutrient absorption.
While researchers have long understood that gut bacteria modify bile acids to activate the FXR receptor, which inhibits bile production, the new study uncovers a different role for the gut microbiota in bile acid regulation. Published on January 8 in Nature, the study identifies a novel enzyme produced by intestinal cells that converts bile acids into a different form, known as bile acid-methylcysteamine (BA-MCY). This altered form of bile acid inhibits FXR, thus promoting bile production and enhancing fat metabolism.
“Our study reveals an ongoing dialogue between gut microbes and the host body, which is critical for regulating bile acid production,” said Dr. David Artis, co-corresponding author of the study and director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.
Bile acids, previously understood primarily as digestive aids, have now been recognized as signaling molecules that influence various metabolic processes, including cholesterol levels and fat metabolism. Dr. Frank Schroeder, co-corresponding author and professor at the Boyce Thompson Institute, explained, “Bile acids regulate cholesterol metabolism and bile acid production by binding to FXR, which acts like a control switch to prevent excess buildup.”
The study, co-led by Dr. Tae Hyung Won, Dr. Christopher Parkhurst, and Dr. Mohammad Arifuzzaman, bridges multiple scientific disciplines, including immunology, chemical biology, and host-microbiota interactions. The researchers employed untargeted metabolomics to identify all the molecules produced by mice with and without gut microbes. This comparison revealed that BA-MCYs were produced by the mice in response to gut microbes, offering a new understanding of how the body controls bile acid production.
Dr. Tae Hyung Won noted, “BA-MCYs are molecules not directly produced by the gut microbes but are still dependent on their presence, offering a new paradigm for understanding this process.”
Through further experiments, the team demonstrated how the body produces BA-MCYs and how these molecules help counteract microbial signals to reduce bile acid production, maintaining a balance that is crucial for healthy cholesterol metabolism.
Dr. Schroeder emphasized the importance of this balance: “When gut bacteria generate large amounts of bile acids that activate FXR, the body produces BA-MCYs to counteract this and maintain equilibrium within the bile acid system.”
The findings suggest that manipulating BA-MCY levels could potentially provide a therapeutic avenue for managing metabolic disorders, such as fatty liver disease, high cholesterol, and obesity-related conditions. Additionally, the study found that increasing dietary fiber intake could boost BA-MCY production, hinting at possible dietary strategies for improving metabolic health.
Dr. Arifuzzaman added, “We also detected BA-MCYs in human blood samples, suggesting that a similar mechanism could be at play in humans.”
This research opens up exciting possibilities for the development of new treatments targeting metabolic diseases, highlighting the critical role of gut microbiota and bile acids in regulating fat metabolism and cholesterol levels.
You Might Be Interested In:
-
Lily Allen Seeks Trauma Treatment After Split from Husband David Harbour
-
New Children’s Hospital in Cambridge to Pioneer Integrated Care for Physical and Mental Health
