Chinese bayberry leaves proanthocyanidins regulate glucose and lipid metabolism associated with the modulation of the gut microbiota-barrier axis

Abstract This study investigated how Chinese bayberry leaves proanthocyanidins (BLPs) regulate glucose and lipid metabolism through the gut microbiota-barrier axis. In high-fat diet (HFD)-induced obese mice, BLPs significantly reduced body weight, improved glucose tolerance, and alleviated dyslipidemia. BLPs remodeled the gut microbiota by reducing the Firmicutes/Bacteroidota ratio and enriching beneficial taxa, including Bifidobacterium and Dubosiella . BLPs also improved intestinal barrier function, as evidenced by increased Occludin and MUC2 expression, reduced serum lipopolysaccharide levels, and enhanced microbial metabolite production, including short-chain fatty acids and altered bile acid profiles. Furthermore, BLPs activated IRS1/PI3K/AKT and AMPK signaling pathways associated with glucose and lipid metabolism. Fecal microbiota transplantation further supported a contribution of the gut microbiota to the metabolic effects of BLPs. These findings provide mechanistic insights into the protective effects of BLPs against HFD-induced metabolic disorders and highlight their potential as functional food ingredients for metabolic health.