Bile acid functions and the role of gut microbiota
Bile acids, derived from cholesterol in the liver, are molecules with detergent-like properties that aid in the digestion of fats and fat-soluble vitamins. After a meal, they are released from the gallbladder into the small intestine, where they emulsify dietary fats for absorption.
To enhance solubility, bile acids are conjugated with amino acids before secretion. Most are reabsorbed at the end of the small intestine, while some are converted by gut microbiota into secondary bile acids, which are passively absorbed in the colon. This enterohepatic circulation ensures that bile acids are recycled, with the liver retrieving them from the bloodstream for reuse.
Research has shown that gut bacteria influence bile acid availability by modifying their structure, while bile acids, in turn, regulate microbial growth through antimicrobial and anti-inflammatory effects both directly and indirectly through farnesoid X receptor (FXR)-induced antimicrobial peptides.
How does gut microbiota promote fat digestion?
Approximately 80% of bile acids remain conjugated as part of the primary bile acids, such as cholic acid (CA) and chenodeoxycholic acid (CDCA). However, certain microorganisms belonging to Lactobacillus genus can deconjugate primary bile acids. Moreover, Clostridioides bacteria perform oxidation and dihydroxylation steps, producing a pool of secondary bile acids. For instance, CA and CDCA are modified by gut microbiota to form deoxycholic acid (DCA) and lithocholic acid (LCA), respectively.
The resulting DCA can reduce bile acid synthesis by activating a liver receptor, known as FXR, complementing the effects of the conjugated bile acids like CA and CDCA. Moreover, both DCA and LCA can bind to intestinal receptors and influence glucose metabolism.
Ultimately, the balance of bile acids maintained by gut microbiota impacts cholesterol homeostasis, fat digestion, and overall metabolic health.
What is the role of gut microbiota in preventing fat accumulation?
Recent findings reveal a complex interplay between the microbiome and its host, involving novel bioactive metabolites. Won et al. discovered bile acids-methylcysteamine (BA-MYC), a molecule abundant in intestinal tissues that inhibits the FXR receptor activity, thereby promoting bile acid production and helping boost fat metabolism.
Studies in mice identified vanin1 (VNN1) as a key protein in BA-MYC production. This process depends on gut microbiota, as free bile acids from microbial metabolism serve as precursors to BA-MYC synthesis. These bile acid conjugates promote bile acid synthesis and, thus, fat metabolism balance based on nutritional status and other factors.
This emerging microbiome-host interaction offers insight into how the microbiota modulates bile acid equilibrium and lipid metabolism, potentially preventing fat accumulation by precisely adjusting bile acid production.
The potential for future nutritional or therapeutic interventions for metabolic diseases
The researchers also showed that boosting BA-MCY levels helped reduce fat accumulation in the liver of mice fed a high-cholesterol diet. Additionally, they found that increasing the intake of dietary fiber, including the fermentable fiber inulin, also enhanced BA-MCY production. Although further research is needed, scientists detected similar BA-MYC molecules in human serum, indicating that these regulatory mechanisms might also occur in humans.
Similarly, certain probiotics, such as Lactobacilli and Bifidobacteria strains, are potential adjuvants in the reduction of serum cholesterol by producing bile salt hydrolases (BSH), which break down conjugated bile salts, decreasing cholesterol reabsorption in the intestine. Recent pilot exploratory human studies have shown that specific strains of Lactiplantibacillus plantarum can modulate bile acid and cholesterol metabolism, reducing blood cholesterol levels.
These findings suggest that food supplementation and microbiota-targeting interventions may prove fruitful in regulating the hepatobiliary system. This opens new avenues for preventive and therapeutic strategies for metabolic diseases such as type II diabetes.
Conclusion and takeaway
As research continues to uncover the intricate relationship between gut microbiota and bile acid regulation in mice and humans, practical steps can already be taken. For instance, adopting a healthy lifestyle, including a Mediterranean diet rich in diverse food groups, probiotics, and dietary fiber, supports a healthy gut microbiota and promotes overall metabolic health.
Reference:
- Won, T.H., Arifuzzaman, M., Parkhurst, C.N. et al. Host metabolism balances microbial regulation of bile acid signalling. Nature. 2025. doi:10.1038/s41586-024-08379-9
- Majait S, Nieuwdorp M, Kemper M, Soeters M. The Black Box Orchestra of Gut Bacteria and Bile Acids: Who Is the Conductor?. Int J Mol Sci. 2023. 24(3):1816. Published 2023 Jan 17. doi:10.3390/ijms24031816
- Fuchs, C.D., Trauner, M. Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology. Nat Rev Gastroenterol Hepatol. 2022. 19, 432–450. doi:10.1038/s41575-021-00566-7
- Lee, M.H., Nuccio, SP., Mohanty, I. et al.How bile acids and the microbiota interact to shape host immunity. Nat Rev Immunol. 2024. 24, 798–809. doi:10.1038/s41577-024-01057-x
- Padro T, Santisteban V, Huedo P, Puntes M, Aguiló M, Espadaler-Mazo J, Badimon L. Lactiplantibacillus plantarum strains KABP011, KABP012, and KABP013 modulate bile acids and cholesterol metabolism in humans. Cardiovasc Res. 2024.120(7):708-722. doi:10.1093/cvr/cvae061
- Öner Ö, Aslim B, Aydas SB. Mechanisms of Cholesterol-Lowering Effects of Lactobacilli and Bifidobacteria Strains as Potential Probiotics with Their bsh Gene Analysis. J Mol Microbiol Biotechnol. 2014. 24(1):12-18. doi: 10.1159/000354316
