Polyphenols ameliorate metabolic disorders by remodeling gut microbiota and regulating Nrf2/NF-κB signaling pathways

Abstract

Intestinal barrier dysfunction, intestinal flora disorder and systemic chronic low-grade inflammation are key pathological processes that drive the progression of a variety of metabolic diseases (including obesity, type 2 diabetes and osteoporosis). Natural polyphenols have the ability to regulate intestinal microecology and regulate multi-target signal transduction, so they show significant metabolic regulation potential in dietary intervention strategies. In view of this, this review takes the pig model (which is highly similar to humans in terms of anatomy, physiology, immunology and intestinal microenvironment) as the research object to explore the intervention effect of polyphenols on metabolic diseases and its transformation clinical value. This review first explains the unique advantages and transformation application prospects of pigs as an ideal large animal model for human metabolic research. Subsequently, the system summarized the molecular mechanism of polyphenols to maintain intestinal homeosta by reshaping the core intestinal flora and promoting the production of short-chain fatty acids (SCFAs). In addition, this review also analyzes the regulatory effect of polyphenols in enhancing systemic antioxidant defense by activating the Nrf2/Keap1 pathway and inhibiting the release of pro-inflammatory factors by blocking the TLR4/NF-κB signaling pathway. By integrating the polyphenol intervention effect observed in the pig model and its potential molecular mechanism, this review provides reliable scientific evidence and theoretical reference for the development of dietary intervention strategies based on natural polyphenols and their subsequent clinical transformation.