The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases

Abstract

The human gut microbiome has been linked to numerous digestive disorders, but its metabolic products have been much less well characterized, in part due to the expense of untargeted metabolomics and lack of ability to process the data. In this review, we focused on the rapidly expanding information about the bile acid repertoire produced by the gut microbiome, including the impacts of bile acids on a wide range of host physiological processes and diseases, and discussed the role of short-chain fatty acids and other important gut microbiome-derived metabolites. Of particular note is the action of gut microbiome-derived metabolites throughout the body, which impact processes ranging from obesity to aging to disorders traditionally thought of as diseases of the nervous system, but that are now recognized as being strongly influenced by the gut microbiome and the metabolites it produces. We also highlighted the emerging role for modifying the gut microbiome to improve health or to treat disease, including the "engineered native bacteria'' approach that takes bacterial strains from a patient, modifies them to alter metabolism, and reintroduces them. Taken together, study of the metabolites derived from the gut microbiome provided insights into a wide range of physiological and pathophysiological processes, and has substantial potential for new approaches to diagnostics and therapeutics of disease of, or involving, the gastrointestinal tract.

Keywords: Bile Acid; Engineered Native Bacteria; Gut–Brain Axis; Irritable Bowel Syndrome; Metabolome; Microbiome; Short-Chain Fatty Acid.

Figure 1.

Bacterial BA biotransformations. Cholesterol is converted to primary BAs in the liver. Primary BAs are conjugated with primarily taurine in mice or glycine in humans before being transported to the gallbladder for storage in the form of bile. On ingestion of dietary fats, primary conjugated BAs (within bile) are released into the gut lumen to aid lipid absorption. Bacteria with BSH deconjugate BAs, thereby weakening their soap-like qualities. This allows other microbiome members to further modify them into secondary BAs. Some secondary BAs can be transported back to the liver, where they are then conjugated. The interaction between the gut microbiome and BAs leads to modulation of FXR and TGR5 agonists and antagonists, and thus, allows the gut microbiome to affect host metabolism. T, taurine; G, glycine. In humans: TCA, taurocholic acid; TCDCA, taurochenodeoxycholic acid. In mice: TαMCA, tauro-α-uricholic acid. Created with BioRender.com.

Figure 2.

Microbially produced SCFAs and their key effects on host metabolism and digestive disease processes. Butyrate, acetate, and propionate are the 3 main SCFAs produced when gut microbes ferment nondigestible dietary fiber in the large intestine. The cecum and proximal colon have the highest concentration of SCFAs, with a decreasing concentration toward the distal colon. The key roles that the 3 main SCFAs play in processes related to digestive diseases and host metabolism that are highlighted in the article are described. GPR43, G protein–coupled receptor 43/free fatty acid receptor 2; GPR41, G protein–coupled receptor 41/free fatty acid receptor 3); IGN, intestinal gluconeogenesis. Created with BioRender.com.