Gut Microbiota-Targeted Polyphenol Interventions: A Novel Paradigm and Synergistic Strategies for Obesity Management.

Abstract

Obesity has emerged as a major metabolic disorder threatening global public health, with gut microbiota (GM) dysbiosis recognized as a key pathogenic driver. While existing reviews have explored associations between GM and obesity (e.g., the gut-liver axis), this review focuses specifically on polyphenols to establish a novel paradigm of "GM-targeted polyphenol interventions." Naturally occurring polyphenols exhibit unique advantages in obesity management; however, their systemic effects critically depend on GM-mediated biotransformation. Herein, we propose the "Polyphenol-GM Axis" as the core mechanism underpinning polyphenol efficacy against obesity, synthesizing and integrating current evidence. This comprehensive review elucidates how polyphenols from diverse sources ameliorate obesity through GM modulation: (1) remodeling gut-liver crosstalk via bile acid metabolism; (2) inhibiting lipogenesis through GM-derived metabolites; (3) restoring intestinal barrier integrity; (4) blocking inflammatory cascades. We elucidate causal relationships between polyphenol-induced GM shifts and host metabolic outcomes, revealing targeted pathways for bidirectional "microbiota-host" regulation. Critically, we propose that combining GM-targeted polyphenol interventions with lifestyle modifications (diet/exercise) enables precision nutrition. This paradigm provides a theoretical foundation for developing polyphenol-based therapeutics beyond nutritional supplements. Future research should prioritize personalized GM modulation and structural optimization of polyphenols to accelerate their translation from functional foods to clinical agents for obesity management.