Effect of a polyphenol-rich dietary pattern on subjects aged ≥ 60 years with higher levels of inflammatory markers: insights into microbiome and metabolome

<b>Background:</b> Aging may be associated with low-grade chronic inflammation ("inflammaging") and gut microbiome alterations. Dietary polyphenols have been proposed as modulators of these processes. This study aimed to explore the effects of a polyphenol-rich diet (PR-diet) on inflammatory markers, gut microbiota, and metabolomic profiles in subjects aged ≥ 60 years stratified by baseline inflammation levels. <b>Methods:</b> In this post-hoc analysis of the MaPLE (Microbiome mAnipulation through Polyphenols for managing Leakiness in the Elderly) randomized crossover trial, 50 subjects aged ≥ 60 years were categorized into two subgroups: high inflammation (cH) and low inflammation (cL). Participants received a PR-diet or a control diet for 8 weeks, with a washout period in between. Fecal, blood, and urine samples were analyzed using shallow shotgun metagenomics and untargeted metabolomics. <b>Results:</b> The PR-diet was associated with a significant reduction in key inflammatory markers [e.g., interleukin-6 (IL-6), C-reactive protein] in the cH group. Distinct microbial shifts were observed, including an increase in <i>Blautia</i> and <i>Dorea</i> and a modest improvement in microbial diversity in cH subjects. Metabolomic analysis revealed group-specific changes, notably in polyphenol-derived metabolites. <b>Conclusion:</b> These findings suggest that PR-diets may beneficially modulate inflammation and the gut microbial ecosystem in subjects aged ≥ 60 years with elevated baseline inflammation. Stratification by inflammatory status may improve the targeting and personalization of dietary interventions to support healthy aging.