Interplay between (poly)phenols, gut microbiota, and biological rhythms: outlook for a new paradigm in brain health

Dietary (poly)phenols, bioactive compounds abundantly found in plant-based foods, undergo extensive metabolism by the host and its gut microbiota, producing metabolites that influence systemic and brain health. Despite their low bioavailability, (poly)phenols have been consistently associated with neuroprotective benefits, such as reducing neuroinflammation and enhancing gut-brain communication. Additionally, circadian rhythms can influence (poly)phenol bioactivity, while these compounds, in turn, modulate biological rhythms. The gut microbiota's diurnal oscillations affect (poly)phenol metabolism and modulate (poly)phenols' effects by producing bioactive metabolites, adding complexity to their health impact. Understanding these mechanisms can aid in designing functional foods and precision nutrition strategies to enhance neuroprotection. However, critical questions remain unanswered. This review explores the interplay between (poly)phenols, circadian rhythms, and gut microbiota, highlighting their collective role in brain health. The influence of individual gut microbiota profiles, polyphenol-related metabotypes, and circadian synchrony on (poly)phenol metabolism and neuroprotection is not fully understood. Likewise, the timing of (poly)phenol consumption and its interaction with rhythmic microbial processes require further exploration. Addressing these gaps could lead to targeted dietary interventions. Future research should prioritize human trials and multi-omics approaches to unravel these complex relationships, advancing precision health strategies that foster cognitive resilience and reduce neurodegenerative disease risk.