Integrative Gut Microbiota and Serum Metabolomics Reveal the Intervention Effect of Quercetin on Type 2 Diabetes

Abstract This study aimed to investigate how quercetin alleviates type 2 diabetes mellitus (T2DM) symptoms in diet-induced T2DM rats by regulating gut microbiota and serum metabolomics. Male Sprague-Dawley rats were divided into four groups: Control, Diabetes, Diabetes + Quercetin, and Control + Quercetin. After 18 weeks of intervention, biochemical parameters, liver histopathology, gut microbiota, and serum metabolomics were analyzed. Results showed quercetin reduced fasting blood glucose, improved lipid profiles and alleviated liver damage in DM rats. It also reversed T2DM-induced decreases in gut microbiota diversity and modulated microbial composition. Metabolomics revealed quercetin decreased SM(d18:1/24:1) and enriched pathways like sphingolipid metabolism. Integrated analysis linked microbiota to metabolites and biochemical parameters. g_Alistipes was negatively correlated with FBG and SM(d18:1/24:1). In conclusion, quercetin exerts distinct anti-diabetic effects in diet-induced T2DM rats by remodeling gut microbiota composition and regulating serum metabolomic profiles. Furthermore, deciphering the crosstalk between quercetin-modulated gut microbial taxa and key metabolic pathways deepens our understanding of the microbiota-metabolite axis in mediating diabetic phenotypes.