Gut feelings in the islets: The role of the gut microbiome and the FFA2 and FFA3 receptors for short chain fatty acids on β-cell function and metabolic regulation.

Short-chain fatty acids (SCFAs) are biosynthesized via fermentation of polysaccharides by gastrointestinal microbiota and have been shown to have wide-reaching effects on almost all tissues, including the pancreatic islets. Historically, the effects of SCFAs have been attributed to their intracellular metabolism and function as energy sources, but the discovery of free fatty acid G protein-coupled receptors (GPCRs) in the 2000s suggested that many functional outcomes of SCFAs are receptor-mediated. The SCFA receptors FFA2/GPR43 and FFA3/GPR41 are expressed on β-cells, where they regulate glucose-dependent insulin secretion, making them attractive targets for treatment of diabetes and other metabolic disorders. Here, we provide an update on the current evidence regarding regulation of FFA2/FFA3 receptors by specific probiotic bacterial species within the gut microbiome that synthesize SCFAs. We also review the body of research regarding the FFA2- and FFA3 receptor-specific function of SCFAs on β-cells and discuss the somewhat controversial and opposing findings within these studies.