Epigallocatechin gallate prevents and alleviates type 2 diabetes mellitus (T2DM) through gut microbiota and multi-organ interactions in Wistar healthy rats and GK T2DM rats.

Abstract

INTRODUCTION: As the main active ingredient of the first FDA-approved phytochemical drug, epigallocatechin gallate (EGCG) can effectively alleviate glucolipid metabolic disorders. However, existing studies mainly focuses on the treatment of EGCG in disease models, with limited focus on its preventive effect on diseases in healthy models. OBJECTIVES: This study investigated how EGCG prevents and alleviates T2DM through gut microbiota and multi-organ interactions in Wistar healthy rats and GK T2DM rats. METHODS: The GK T2DM rat strain was established through repeated selective breeding of Wistar rats with glucose intolerance. Whether and how EGCG prevents and alleviates T2DM were evaluated, including glucose production and absorption efficiency, glucose transport, glucose metabolism, glucose excretion, T2DM-related tissue damage, gut microbiota, and liver transcriptome. RESULTS: The health benefits of EGCG are primarily reliant on the involvement of the gut microbiota. Our study showed that although the specific microbial communities involved differ, the bidirectional interaction between EGCG and gut microbiota is widespread in healthy rats and T2DM rats. EGCG intervention elevated the relative abundance of specific microbial communities, which in turn promoted the metabolic processing of EGCG in the gut, producing numerous EGCG metabolites that may contribute to preventing and alleviating T2DM. In healthy rats, EGCG intervention selectively enhanced insulin secretion and serum insulin levels to prevent T2DM. In T2DM rats, EGCG intervention selectively lowered blood glucose levels, improved insulin resistance, delayed glucose production and absorption, and promoted urinary glucose excretion to alleviate T2DM. In both healthy and T2DM rats, EGCG intervention universally reduced gut microbiota-derived lipopolysaccharides, maintained systemic oxidative stress homeostasis, alleviated liver and kidney damage, increased muscle glycogen content, and promoted beige thermogenesis in white fat, thus demonstrating potential for preventing and alleviating T2DM. CONCLUSION: As a natural active ingredient, EGCG could prevent and alleviate T2DM through gut microbiota and multi-organ interactions.