MaPLE insights into microbiome and metabolome.
The intake of polyphenol-rich foods may represent a promising strategy to preserve intestinal barrier integrity. A polyphenol-rich diet (PR-diet) could therefore be particularly important for older people, who are characterized by higher intestinal permeability and “inflammaging”. The present study has been developed in the context of the project entitled “Microbiomics mAnipulation through Polyphenols for managing the Leakiness in the Elderly” (MaPLE), funded by the European Joint Programming Initiative – “A Healthy Diet for a Healthy Life”. The MaPLE project conducted an 8-week, randomized, controlled dietary intervention study comparing the physiological parameters and metabolites derived from serum, urine, and feces between participants following a PR-diet and those following a standard Control diet. The inflammatory markers in serum (CRP, TNF-a, IL-6, calprotectin) and feces (calprotectin) were measured. Based on these markers using clustering algorithm it has been noted that older individuals were stratified in two clusters (R:0.49; P=0.01): the high (cH) and low (cL) inflammatory level clusters. The microbiome diversity analyzed by shallow shotgun metagenomics significantly predicted the two clusters (AUC: 0.96). The results showed the ability of PR-diet to decrease several physiological parameters in cH volunteers (triglycerides, AST, and serum calprotectin). In addition, the PR-diet modulated the a-diversity (increasing of CHAO1 index) and taxonomic composition of the fecal microbiome in the cH group inducing the expansion of the genus Blautia, and the species Anaerobutyricum (formerly Eubacterium) hallii, Anaerostipes hadrus, Ruminococcus gnavus, and Dorea formicigenerans. Additionally, the PR-diet had an impact on the levels of several metabolites in serum (including asymmetric-dimethylarginine, phenylacetylglutamine, xanthosine, oleoyl-carnitine, 4-4-methyl-2-oxovaleric, Ergothioneine, and ascorbic acid), urine (1-O-methylpyrogallol, dihydroresveratrol 4'-glucuronide, 2-hydroxybenzoic acid, methyl(epi)catechin, and N-acetyl-S-allylcysteine), and feces (tryptophan). These metabolites were found to be significantly different between the two groups. Furthermore, gene prediction analysis revealed differences in two pathways (thiazole biosynthesis and inosine-5'-phosphate biosynthesis III) that were negatively and positively correlated with inflammatory markers, respectively. In summary, these findings from the clusterization of volunteers in two groups, aligned with the bacterial composition of the fecal microbiota, suggest a robust association between inflammaging, the intestinal microbiome and metabolites.  This research enhances our understanding of the complex relationship between diet, the microbiome, and inflammation in aging, offering opportunities for the development of new avenues in dietary interventions to promote healthy aging.