Mulberry polyphenols restored both small and large intestinal microflora in db/db mice, potentially alleviating type 2 diabetes

Abstract

Polyphenols in mulberry fruit have potential antidiabetic effects by targeting gut microbiota. This study investigated how mulberry polyphenols (MP) influence the microbiota of the small and large intestines and their effects on type 2 diabetes symptoms. The results showed lower microbiota densities in the small intestine. MP treatments improved microbiota richness and diversity in both intestines, similarly to metformin. Particularly, at 400mg/kg dose, mulberry polyphenols decreased Firmicutes, Lactobacillus, and Bacilli, while increasing Bacteroidetes, leading to elevated propionate and butyrate levels. Less abundant small intestine microbiota, like Enterobacteriales, Mycoplasmatales, Enterobacteriaceae, and Ureaplasma, were involved in regulating blood glucose and insulin levels. Functional analysis suggested that mulberry polyphenols reshaped the small intestine microbiota to influence blood glucose balance via unknown pathways, while in the large intestine, they primarily affect blood glucose through carbohydrate transport and metabolism. Based on its ability to regulate the composition of intestinal flora, MP likely improved glucose homeostasis by enhancing glucose utilization, supporting pancreatic tissue health, and increasing serum antioxidant capacity. However, the specific mechanisms underlying this potential are yet to be fully explored. This study provided new insights into the influence of MP on remodeling the microbiota residing in both the small and large intestine, which thereby may be contributed to the improvement of the pathophysiology of type 2 diabetes.