Synergistic Effects of Polyphenols and Gut Microbiota–Derived Metabolites on Inflammation and Metabolic Syndrome: A Review

Polyphenols, a diverse group of phytochemicals abundant in plant-derived foods, are being increasingly recognized for their regulatory effects on inflammation and metabolic disorders. Their interaction with the gut microbiota (GM) is complex and bidirectional: Polyphenols influence microbial composition by promoting the growth of beneficial bacteria and inhibiting pathogenic strains, while gut microbes metabolize polyphenols into bioactive metabolites that enhance their bioavailability. This dynamic interaction has profound implications for host metabolism, inflammation regulation, and disease prevention. Polyphenol-rich dietary sources, such as tea, berries, grapes, and pomegranates, exert prebiotic-like effects by selectively enriching commensal bacteria, including Lactobacillus and Bifidobacterium spp., while downregulating harmful genera such as Clostridium. These compounds attenuate inflammatory responses through the modulation of intracellular signaling cascades, suppression of pro-inflammatory cytokines, and mitigation of oxidative stress via activation of anti-oxidant pathways. Despite growing evidence supporting the beneficial health effects of polyphenols and their microbiota-derived metabolites, further mechanistic and longitudinal studies are warranted to elucidate the specific pathways involved and to assess their long-term impact on human health. This review highlights the role of polyphenols and gut-associated metabolites on various inflammatory pathways and associated metabolic syndrome.