Gut Microbiota–Derived Metabolites of Dietary Polyphenols in Cognitive Aging: Bioavailability, Neuroinflammation, and Precision Nutrition Implications

Abstract

Cognitive aging, the age-related degeneration of cognitive ability, is an increasing global health issue, with diet becoming a variable to work on its course. Despite established neuroprotective properties of dietary polyphenols, most of the parent compounds have poor systemic bioavailability, prohibiting their direct action in the central nervous system (CNS). Recent studies have redirected interest to microbiota-derived catabolites; urolithins, equol, enterolignans, phenolic acids, and short-chain fatty acids (SCFAs) that are less toxic and can enter the systemic circulation and possibly cross the blood-brain barrier (BBB). This review identifies polyphenols-derived microbial metabolites as those that are generated by the gut rather than parent polyphenols. Cellular, animal, and limited human evidence implicates these metabolites in cellular neuroinflammation regulation and mitochondrial functioning in cognitive aging, albeit with varying strengths and limitations. Previous studies mainly focused on parent compounds even though most polyphenols reach the colon in their original form, where they are converted to bioactive metabolites with greater bioavailability by gut microbes. This has made these metabolites appear to be the major mediators of health benefits, and this emphasizes the need of microbial transformation processes. Nonetheless, there are still gaps, such as sparse clinical data and a high inter-individual disparity on metabolite production caused by microbiome disparities. The review also differentiates between cognitive aging, cognitive decline, and mild cognitive impairment (MCI) and marks the necessity of metabotype-based precision nutrition approaches.