Host bile acid and short-chain fatty acid receptors

Host bile acid and short-chain fatty acid (SCFA) receptors are a diverse group of proteins that sense metabolites produced by the gut microbiota, serving as a critical link in the gut-liver and gut-brain axes (Trauner et al., 2010). This group includes nuclear receptors like the Farnesoid X receptor (FXR) and G protein-coupled receptors like TGR5 (GPBAR1) for bile acids, as well as FFAR2 (GPR43) and FFAR3 (GPR41) for SCFAs (Xie et al., 2022). These receptors play fundamental roles in regulating energy homeostasis, lipid and glucose metabolism, and immune system modulation (Cariello et al., 2021). Dysregulation of these signaling pathways is implicated in various conditions, including nonalcoholic steatohepatitis (NASH), primary biliary cholangitis (PBC), obesity, and inflammatory bowel disease (Jiao et al., 2022). Therapeutic strategies often involve the use of agonists, such as the FDA-approved obeticholic acid for FXR, to improve metabolic parameters and reduce hepatic inflammation (Frontiers in Pharmacology, 2022). However, targeting these receptors can lead to side effects like pruritus or altered lipid profiles, necessitating careful drug design and patient monitoring (Trauner et al., 2010). Overall, these receptors are pivotal targets for managing metabolic and inflammatory disorders through the modulation of host-microbe interactions.

Other names

Microbiota-derived metabolite receptorsBile acid receptorsShort-chain fatty acid receptorsFarnesoid X receptor (FXR)G protein-coupled bile acid receptor 1 (GPBAR1)TGR5Free fatty acid receptor 2 (FFAR2)GPR43Free fatty acid receptor 3 (FFAR3)GPR41Hydroxycarboxylic acid receptor 2 (HCAR2)GPR109APregnane X receptor (PXR)Vitamin D receptor (VDR)

Agonism of nuclear receptors (e.g., FXR) and G protein-coupled receptors (e.g., TGR5, FFAR2, FFAR3) to modulate metabolic, inflammatory, and endocrine signaling pathways.