Dendrobium nobile Lindl. Polysaccharides ameliorate the inflammatory microenvironment in the retina of diabetic rats: a multi-omics study of the gut-blood-retina axis.

The global epidemic of type 2 diabetes (T2D) and its complications threaten human health and lives. Dendrobium nobile Lindl., a traditional Chinese medicinal herb, demonstrates anti-hyperglycemic and anti-hyperlipidemic effects. However, its protective role and mechanisms against diabetes-induced retinopathy remain unclear. This study aimed to investigate the impact of Dendrobium nobile Lindl. Polysaccharides (DNP) on the gut microbiota-metabolite-retinal inflammatory microenvironment in T2D rats. The results demonstrated that DNP could significantly ameliorate hyperglycemia, restore gut microbiota, and improve related microbial metabolites. Interestingly, DNP restored the damaged gut barrier and improved the metabolic profiles of circulating amino and organic acids. Specifically, DNP decreased the Firmicutes/Bacteroidota (F/B) ratio, restored gut morphology and the expression of ZO-1 and claudin-1, reduced serum lipopolysaccharides (LPS) levels, decreased gut and circulating branched-chain amino acids (BCAA) metabolism, increased gut and circulating hippurate metabolism, inhibited the TLR4/NF-κB signaling pathway, and ultimately ameliorated the inflammatory microenvironment of the retina. This comprehensive multi-omics study provides the first systematic evaluation of the therapeutic effects of DNP on T2D and its associated retinal inflammatory microenvironment, proposing the "gut-blood-retina" axis as a key mechanistic pathway. Consequently, DNP treatment emerges as a promising preventive or therapeutic strategy for mitigating these pathophysiological processes.