Lycium barbarum glycopeptide alleviates diabetic retinopathy by modulating the gut microbiota and metabolites

Diabetic retinopathy, a vision-threatening complication of diabetes, is closely linked to gut microbiota dysbiosis through the microbiota-gut-retina axis, which drives inflammation and retinal damage. Lycium barbarum glycopeptide exhibits retinal protective effects, but its role in modulating this axis in diabetic retinopathy remains unclear. This study explored the therapeutic potential of Lycium barbarum glycopeptide in diabetic retinopathy and its underlying mechanisms related to modulation of the microbiota-gut-retina axis. Treatment of db/db mice with Lycium barbarum glycopeptide ameliorated retinal structure and function, increased retinal tight junction proteins, reduced retinal inflammation, and inhibited the activation of microglial cells and Müller cells. It also restored intestinal tight junction proteins, alleviated endotoxemia, and modulated the Toll-like receptor 4/protein kinase B/ mechanistic target of rapamycin signaling pathway. Moreover, Lycium barbarum glycopeptide alleviated gut microbiota dysbiosis, improving microbial diversity and composition, reducing pro-inflammatory bacterial taxa while increasing beneficial species, and mitigating plasma metabolite profiles. According to the findings, we speculate that Lycium barbarum glycopeptide may alleviate diabetic retinopathy by targeting the Toll-like receptor 4/protein kinase B/mechanistic target of rapamycin signaling pathway. The restoration of gut microbiota dysbiosis and the alleviation of endotoxemia may play a significant role in its therapeutic effects. These results confirm the critical role of the microbiota-gut-retina axis in the pathogenesis of diabetic retinopathy, suggesting that this axis holds promise as a novel therapeutic target for diabetic retinopathy.