Abstract

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. 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. 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. 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. ISRCTN10214981.

Highlights

  • Background &aimThe MaPLE study was a randomized, controlled, crossover trial involving adults !60 y.o. (n 1⁄4 51) living in a residential care facility during an 8-week polyphenol-rich (PR)-diet

  • In the MaPLE trial, we found that an 8-week polyphenol-rich (PR) diet comprising 3 daily portions of PR-foods such as cocoa, green tea and berries (1391 mg/day of dietary polyphenols vs. 812 mg/day registered in the control diet) led to a significant reduction of the intestinal permeability (IP) marker, zonulin, in older subjects affected by “leaky gut” [16]

  • In the Mixed Graphical Model (MGM) network, the increase of catechol sulfate (CAT-S), 7-MX and TB and the decrease of deoxycarnitine levels were correlated with baseline zonulin, and not with its changes, showing that the effects of the intervention on these metabolites depended on higher extent on baseline IP

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Summary

Introduction

Background &aimThe MaPLE study was a randomized, controlled, crossover trial involving adults !60 y.o. (n 1⁄4 51) living in a residential care facility during an 8-week polyphenol-rich (PR)-diet. The MaPLE study was a randomized, controlled, crossover trial involving adults !60 y.o. 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. 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. 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.

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