Probiotic–polyphenol synergy: Emerging insights for gut microbiome health and functional food design

ABSTRACT The bidirectional interactions between probiotics and dietary polyphenols have emerged as a promising strategy for modulating the gut microbiota and developing next-generation functional foods. Although probiotics and polyphenols have been extensively investigated individually, their reciprocal mechanisms, clinical evidence, formulation strategies, and translational potential have not been comprehensively synthesized within a unified framework. This review critically evaluated current evidence on probiotic-polyphenol synergy, with emphasis on molecular mechanisms, microbial biotransformation, functional food design, preclinical and clinical evidence, regulatory considerations, and future research directions. Current evidence demonstrates that dietary polyphenols function as prebiotic-like modulators by selectively enriching beneficial microorganisms while suppressing opportunistic pathogens, whereas probiotic microorganisms enzymatically convert poorly bioavailable polyphenols into bioactive metabolites with enhanced absorption and biological activity. These complementary interactions improve microbial metabolite production, including short-chain fatty acids (SCFAs), reinforce intestinal barrier integrity, regulate immune and inflammatory pathways, and contribute to metabolic homeostasis. Despite encouraging mechanistic and experimental findings, clinical translation remains constrained by substantial heterogeneity in probiotic strains, polyphenol composition, food matrices, intervention protocols, dosage, and host-specific microbiota profiles. This review further highlights recent advances in encapsulation technologies, microbiome-targeted functional food formulation, multi-omics, systems biology, and artificial intelligence (AI)-assisted analytical approaches that may facilitate precision nutrition and rational product development. However, these emerging technologies require rigorous experimental validation and standardized clinical evaluation before routine application. Future progress will depend on integrated multidisciplinary research combining standardized probiotic strain characterization, chemically defined polyphenol preparations, harmonized intervention protocols, and well-designed multicenter clinical trials. Such efforts will accelerate the translation of probiotic-polyphenol synergy into scientifically validated, safe, and personalized microbiome-targeted functional foods for improving human health.