Rutin alleviates dietary advanced glycation end products (AGEs)-induced insulin resistance in mice by modulation of gut microbiota

Abstract

Dietary advanced glycation end products (AGEs), formed during thermal food processing, are associated with metabolic disorders. This study investigated the efficacy of rutin in alleviating AGEs-induced insulin resistance (IR) in a mouse model. Male C57BL/6 mice were fed a high-AGEs diet for 12 weeks to induce IR, followed by 8 weeks of rutin intervention. Rutin supplementation markedly ameliorated IR, as indicated by reduced hyperglycemia and dyslipidemia, a reduced homeostasis model assessment of insulin resistance (HOMA-IR) index, an elevated insulin sensitivity (HOMA-IS) index, and upregulation of insulin receptor substrates IRS-1 and IRS-2.Metagenomic analysis demonstrated that rutin intervention restored gut microbial richness and diversity and induced structural shifts in the microbiota composition. Specifically, rutin enriched beneficial genera, including Akkermansia, Bifidobacterium, Faecalibacterium, Lactobacillus, and Coriobacteriales, while reducing populations of IR-associated taxa such as Erysipelotrichaceae, Coprobacillus, Enterococcus, Adlercreutzia, and Allobaculum. Concurrently, rutin increased fecal concentrations of short-chain fatty acids (SCFAs), notably acetic acid and propionic acid. Spearman's correlation analysis confirmed negative associations between rutin-modulated microbiota and IR indicators. These results demonstrate that rutin mitigates AGEsinduced IR by reshaping the gut microbiome and promoting beneficial microbial metabolites.