Paeonidin- and Cyanidin-Rich Fractions Ameliorate Gut Microbiota and Serum Metabolites in Rats with Type 2 Diabetes

Background: Dietary intervention could modulate gut microbiota, improve insulin resistance status, and play a key role in blood glucose regulation. Objective: This study investigated the regulatory effects of paeonidin- and cyanidin-rich fractions (PCs) on gut microbiota and serum metabolites in high-fat, high-sucrose diet/streptozotocin-induced type 2 diabetes mellitus (T2DM) rats. Method: Following a 14-day intragastric PC administration (25 mg/kg/day), non-targeted metabolomics and 16S rDNA sequencing were performed. Results: PC intervention significantly reduced water intake, and even the effects on lipids were limited. Among 83 differential serum metabolites, PC restored 28, including tauroursodeoxycholic acid (TUDCA) and lysophosphatidylcholines, while decreasing glycated branched-chain amino acid derivatives. PC-enriched Bifidobacterium, Sediminibacterium, SC-I-84, and Fusicatenibacter, which positively correlated with TUDCA. Additionally, PC upregulated insulin secretion and p53 signaling pathways with increased RYR2 and FAS, while downregulating pentose and glucuronate interconversion enzymes (UxaC, XylB). Conclusions: These findings suggest that the amelioration of glycolipid metabolic disorders and insulin secretion defects by PC may be associated with a synergistic gut microbiota-metabolite-enzyme axis, potentially involving Bifidobacterium-mediated TUDCA elevation and downstream modulation of metabolic enzymes.