The study investigates the role of short-chain fatty acids (SCFAs) and the G-protein-coupled receptor 43 (GPR43) in regulating inflammatory responses. SCFAs, produced by the fermentation of dietary fiber by gut microbiota, have been shown to have anti-inflammatory properties. The researchers found that SCFAs bind to GPR43, which is expressed on immune cells involved in inflammation. GPR43-deficient mice (Gpr43−/−) showed exacerbated inflammation in models of colitis, arthritis, and asthma compared to wild-type mice. Treatment with SCFAs, particularly acetate, protected against these inflammatory conditions in Gpr43−/− mice. The study also revealed that GPR43 signaling affects several signaling pathways associated with inflammation, cell migration, and apoptosis. These findings suggest that SCFA-GPR43 interactions may represent a central mechanism by which commensal bacteria regulate immune and inflammatory responses, and could be a potential target for therapeutic interventions.The study investigates the role of short-chain fatty acids (SCFAs) and the G-protein-coupled receptor 43 (GPR43) in regulating inflammatory responses. SCFAs, produced by the fermentation of dietary fiber by gut microbiota, have been shown to have anti-inflammatory properties. The researchers found that SCFAs bind to GPR43, which is expressed on immune cells involved in inflammation. GPR43-deficient mice (Gpr43−/−) showed exacerbated inflammation in models of colitis, arthritis, and asthma compared to wild-type mice. Treatment with SCFAs, particularly acetate, protected against these inflammatory conditions in Gpr43−/− mice. The study also revealed that GPR43 signaling affects several signaling pathways associated with inflammation, cell migration, and apoptosis. These findings suggest that SCFA-GPR43 interactions may represent a central mechanism by which commensal bacteria regulate immune and inflammatory responses, and could be a potential target for therapeutic interventions.