Abstract
Bile acids (BAs) are produced from cholesterol in the liver and are termed primary BAs. Primary BAs are conjugated with glycine and taurine in the liver and then released into the intestine via the gallbladder. After the deconjugation of glycine or taurine by the gut microbiome, primary BAs are converted into secondary BAs by the gut microbiome through modifications such as dehydroxylation, oxidation, and epimerization. Most BAs in the intestine are reabsorbed and transported to the liver, where both primary and secondary BAs are conjugated with glycine or taurine and rereleased into the intestine. Thus, unconjugated primary Bas, as well as conjugated and unconjugated secondary BAs, have been modified by the gut microbiome. Some of the BAs reabsorbed from the intestine spill into the systemic circulation, where they bind to a variety of nuclear and cell-surface receptors in tissues, whereas some of the BAs are not reabsorbed and bind to receptors in the terminal ileum. BAs play crucial roles in the physiological regulation of various tissues. Furthermore, various factors, such as diet, age, and antibiotics influence BA composition. Here, we review recent findings regarding the physiological roles of BAs modified by the gut microbiome in the metabolic, immune, and nervous systems.
Highlights
Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki 769-2193, Laboratory of Neuroendocrinology, Institute of Neuroscience, Tokushima Bunri University, Shido 1314-1, Sanuki 769-2193, Kagawa, Japan
18 In brain of humans and rodents, Bile acids (BAs) can affect the nervous system this review, we address the current knowledge on the physiological role of BAs modified by the gut microbiome in the metabolic, immune, and nervous systems
Nuclear receptors regulated by BAs include the constitutive androstane receptor (CAR), pregnane X receptor (PXR), vitamin D receptor (VDR), liver X receptor (LXR), and glucocorticoid receptor (GR)
Summary
Bile acids (BAs) are amphipathic steroid acids produced from cholesterol in the liver, and de novo synthesized bile acids in the liver are termed primary BAs. BAs reabsorbed from the gut are transported to the liver through the portal vein, they are conjugated with glycine and taurine in the liver and are secreted into the bile again for enterohepatic circulation (Figure 1). Recent studies suggest that BAs are hormones or signaling molecules because they can bind to several nuclear and cell-surface receptors, including farnesoid X receptor (FXR) and Takeda G protein receptor 5 (TGR5)— known as G protein-coupled bile acid receptor 1 (GPBAR1) [3,4] By activating these receptors, BAs can regulate BA, glucose, and lipid metabolism in various tissues, including the liver, pancreas, and both brown and white adipose tissue [5]. By bile acid-inducible (bai) operon genes of gut bacteria, CA and CDCA are dehydrogenated and converted to deoxycholic acid (DCA).
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