Dietary capsaicin attenuates type 2 diabetes via gut microbiota and bile acid metabolic pathways

Diabetes is a serious global health concern. Notably, individuals who prefer spicy food exhibit a lower diabetes risk, making the exploration of capsaicin—the pungent compound in chili peppers—highly relevant. The gut microbiota and its metabolites are key targets in diabetes management. This study demonstrates that dietary capsaicin alleviates type 2 diabetes (T2D) in mice. It reduces intestinal levels of conjugated bile acids (e.g., TDCA, GCA, TCA) and normalizes abundance of bile acid-related bacteria, Parabacteroides and Lactobacillus . Capsaicin also lowers the compensatory increase of intestinal bile salt hydrolase and regulates the function of bile acid-stimulated receptors. Bioinformatics analysis of ileum gene profiles indicated that regulated genes are primarily linked to immunity. This was confirmed by measuring inflammatory cytokines in serum and pancreas, and by assessing immune-related gene expression in the ileum. In conclusion, capsaicin can prevent and treat T2D by modulating gut microbiota, bile acid metabolism, and inflammatory responses.