Dendrobium officinale leaf phenolic extracts alleviate diabetes mellitus in mice via modulating metabolism and reshaping gut microbiota

Abstract BACKGROUND Diabetes mellitus is a chronic metabolic disorder posing a significant public health challenge. Dendrobium officinale is a valuable edible‐medicinal homologous plant. Phenolic extracts from fermented D. officinale leaves (DOLP) demonstrate a hypoglycemic effect. However, the effects of DOLP on physiological metabolism and gut microbiota under diabetic conditions remain unknown. RESULTS Untargeted metabolomics analysis revealed that DOLP reversed 98 significantly differential metabolites (SDMs) in diabetic mice. Indoxyl sulfate and palmitoyl sphingomyelin were identified as the primary candidate biomarkers associated with the hypoglycemic effect. KEGG pathway enrichment analysis underscored the significance of arginine and proline metabolism, ascorbate and aldarate metabolism, and fatty acid metabolism in the regulatory effects of DOLP. Furthermore, DOLP reversed the dysbiosis of the gut microbiota in diabetic mice, significantly influencing the relative abundance of the genera Intestinimonas , GCA_900066575 , Muribaculum , and Enterorhabdus . These differential genera exhibited various correlations with SDMs, including l ‐hydroxyarginine, γ‐guanidinobutyrate, l ‐threonate, d ‐galactarate, l ‐ascorbic acid, palmitic acid, cis ‐9‐palmitoleic acid, octadecanoic acid, and oleic acid. CONCLUSION The protective effect of DOLP against diabetes mellitus is closely linked to its regulation of physiological metabolism and gut microbiota. DOLP may serve as a promising agent for the prevention and treatment of diabetes mellitus. © 2025 Society of Chemical Industry.