Mechanistic insights into the hypoglycemic effects of polyphenol-rich Saccharum officinarum extract by integrating microbiomics and metabolomics

Sugarcane ( Saccharum officinarum L.) has been recognized for its benefits in blood glucose control; however, its mechanisms of action are not yet fully defined. Here, integrated microbiomics and metabonomics were utilized to elaborate the hypoglycemic mechanisms of sugarcane polyphenol extract (SPE) in a diabetic mouse model. A total of 22 polyphenol compounds were identified in SPE by UPLC-MS/MS, accounting for 20.4% of the extract. Oral administration of SPE ameliorated multiple diabetic manifestations in db/db mice, including hyperglycemia, hyperinsulinemia, dyslipidemia, adipose tissue hypertrophy, tissue lesions, and gut inflammation. Untargeted metabolomic analysis of serum identified key metabolites involved in glycolipid metabolism, such as phosphatidylcholine, 19(S)-HETE, leukotriene D4, citrate, and taurocholic acid. Moreover, 16S rRNA sequencing indicated that the metabolic improvements induced by SPE were linked to a shift in the gut microbiota, characterized by an increase in beneficial taxa (e.g., Alistipes , Ligilactobacillus ) and a decrease in Lachnospiraceae_NK4A136_group and Oscillibacter . Importantly, SPE elevated fecal levels of SCFAs (acetate, propionate, butyrate) and enhanced the activity of their producing enzymes (acetate kinase (Ack), methylmalonyl-CoA decarboxylase (Mcd), and butyryl-CoA (But). Collectively, our findings demonstrate that SPE may exert hypoglycemic effects via remodeling the gut microbiota and metabolites, offering a potential therapeutic strategy for T2D.