A Polyphenol-Rich Diet Increases the Gut Microbiota Metabolite Indole 3-Propionic Acid in Older Adults with Preserved Kidney Function.

SCOPE: Dietary polyphenols can alter the gut microbiota (GM) and promote the production of bioactive metabolites. Several indoles result of GM metabolism of dietary tryptophan have been associated with intestinal barrier integrity. Our aim is to study the changes in GM-derived indoles during a polyphenol-rich (PR) diet intervention in older adults. METHODS AND RESULTS: Randomized, controlled, crossover trial in adults ≥ 60 years living in a residential care facility during an 8-week PR versus control diet (n = 51). Seven GM-tryptophan metabolites are measured in serum, and metataxonomic analysis of GM is performed on fecal samples. Exploratory subgroup analyses are performed based on renal function (RF). The PR-diet significantly increases serum indole 3-propionic acid (IPA) in subjects with normal RF, but not in subjects with impaired RF. Other GM-tryptophan metabolites are not affected. Comparison of baseline GM composition shows shifts in Bacteroidales order members as well as higher abundance of Clostridiales in participants with normal RF. During the trial, variations of IPA are associated with changes in C-reactive protein (ß = 0.32, p = 0.010) and GM, particularly with the Clostridiales (r = 0.35, p < 0.001) and Enterobacteriales (r = -0.15, p < 0.05) orders. CONCLUSION: A PR diet increases the serum concentration of IPA in older adults with normal RF. Our findings may be important when defining appropriate dietary interventions for older adults. TRIAL REGISTRATION NUMBER: ISRCTN10214981 (https://doi.org/10.1186/ISRCTN10214981).

Crosstalk among intestinal barrier, gut microbiota and serum metabolome after a polyphenol-rich diet in older subjects with "leaky gut": The MaPLE trial.

BACKGROUND &AIM: The MaPLE study was a randomized, controlled, crossover trial involving adults ≥60 y.o. (n = 51) living in a residential care facility during an 8-week polyphenol-rich (PR)-diet. Results from the MaPLE trial showed that the PR-diet reduced the intestinal permeability (IP) in older adults by inducing changes to gut microbiota (GM). The present work aimed at studying the changes in serum metabolome in the MaPLE trial, as a further necessary step to depict the complex crosstalk between dietary polyphenols, GM, and intestinal barrier. METHODS: Serum metabolome was monitored using a semi-targeted UHPLC-MS/MS analysis. Metataxonomic analysis (16S rRNA gene profiling) of GM was performed on faecal samples. Clinical characteristics and serum levels of the IP marker zonulin were linked to GM and metabolomics data in a multi-omics network. RESULTS: Compared to the control diet, the PR-diet increased serum metabolites related to polyphenols and methylxanthine intake. Theobromine and methylxanthines, derived from cocoa and/or green tea, were positively correlated with butyrate-producing bacteria (the order Clostridiales and the genera Roseburia, Butyricicoccus and Faecalibacterium) and inversely with zonulin. A direct correlation between polyphenol metabolites hydroxyphenylpropionic acid-sulfate, 2-methylpyrogallol-sulfate and catechol-sulfate with Butyricicoccus was also observed, while hydroxyphenylpropionic acid-sulfate and 2-methylpyrogallol-sulfate negatively correlated with Methanobrevibacter. The multi-omics network indicated that participant's age, baseline zonulin levels, and changes in Porphyromonadaceae abundance were the main factors driving the effects of a PR-diet on zonulin. CONCLUSION: Overall, these results reveal the complex relationships among polyphenols consumption, intestinal permeability, and GM composition in older adults, and they may be important when setting personalized dietary interventions for older adults. TRIAL REGISTRATION NUMBER: ISRCTN10214981.