Host G protein-coupled receptors and nuclear receptors for microbial metabolites

Host G protein-coupled receptors (GPCRs) and nuclear receptors for microbial metabolites are a collective group of proteins that facilitate communication between the gut microbiota and the host. This group includes GPCRs like Free fatty acid receptor 2 (FFAR2) and Free fatty acid receptor 3 (FFAR3), which sense short-chain fatty acids (SCFAs) produced by bacterial fermentation, and G protein-coupled bile acid receptor 1 (GPBAR1/TGR5), which responds to secondary bile acids (Nicholson et al., 2012). It also encompasses nuclear receptors such as the Aryl hydrocarbon receptor (AhR), which detects tryptophan-derived indoles, and the Farnesoid X receptor (FXR), a primary sensor for bile acids (Rooks & Garrett, 2016). These receptors are pivotal in regulating immune cell maturation, maintaining the intestinal epithelial barrier, and coordinating systemic energy metabolism. Dysregulation of these pathways is strongly associated with chronic inflammatory conditions, metabolic disorders like type 2 diabetes and obesity, and certain gastrointestinal cancers. Therapeutic targeting of these receptors, using agents like Obeticholic acid for FXR or Tapinarof for AhR, aims to leverage the beneficial effects of microbial signaling to treat human disease (Postler & Schierwagen, 2021). However, the widespread expression and complex cross-talk of these receptors necessitate careful drug design to avoid off-target effects and systemic toxicity.

Other names

Microbiota-sensing receptorsMetabolite-sensing receptorsMicrobial metabolite receptorsHost-microbe signaling receptors

These receptors function by binding specific microbial-derived ligands, such as short-chain fatty acids or bile acids, which induces conformational changes that trigger intracellular signaling cascades or modulate gene transcription to maintain host-microbe symbiosis (Rooks & Garrett, 2016; Postler & Schierwagen, 2021).