The Polyphenol–Microbiota Axis: Molecular Mechanisms, Metabolic Pathways, and Therapeutic Perspectives in Human Health

Polyphenols are a diverse class of bioactive phytochemicals increasingly recognized for their ability to modulate human physiology through extensive interactions with the gut microbiota. This review provides a comprehensive and updated synthesis of the bidirectional polyphenol–microbiota relationship, emphasizing how dietary polyphenols reshape microbial community structure while intestinal microorganisms metabolize polyphenols into smaller, more bioavailable derivatives. These microbial metabolites—such as urolithins, phenolic acids, and dihydroresveratrol—exert amplified biological activities compared to their parent molecules, acting on key molecular pathways linked to oxidative stress, inflammation, energy homeostasis, and metabolic regulation. Through integration of mechanistic studies, multi-omics analyses, and emerging clinical evidence, this review outlines the potential of the polyphenol–microbiota–metabolite axis as a target for precision nutrition and microbiota-informed therapeutic interventions. The manuscript highlights ongoing challenges, including inter-individual variability in polyphenol metabolism, and proposes future research directions to advance the field of personalized nutrition.