Abstract

Background: Polyphenols are secondary metabolites produced by plants to defend themselves from environmental stressors. We explored the effect of Wolffia globosa ‘Mankai’, a novel cultivated strain of a polyphenol-rich aquatic plant, on the metabolomic-gut clinical axis in vitro, in-vivo and in a clinical trial. Methods: We used mass-spectrometry-based metabolomics methods from three laboratories to detect Mankai phenolic metabolites and examined predicted functional pathways in a Mankai artificial-gut bioreactor. Plasma and urine polyphenols were assessed among the 294 DIRECT-PLUS 18-month trial participants, comparing the effect of a polyphenol-rich green-Mediterranean diet (+1240 mg/polyphenols/day, provided by Mankai, green tea and walnuts) to a walnuts-enriched (+440 mg/polyphenols/day) Mediterranean diet and a healthy controlled diet. Results: Approximately 200 different phenolic compounds were specifically detected in the Mankai plant. The Mankai-supplemented bioreactor artificial gut displayed a significantly higher relative-abundance of 16S-rRNA bacterial gene sequences encoding for enzymes involved in phenolic compound degradation. In humans, several Mankai-related plasma and urine polyphenols were differentially elevated in the green Mediterranean group compared with the other groups (p < 0.05) after six and 18 months of intervention (e.g., urine hydroxy-phenyl-acetic-acid and urolithin-A; plasma Naringenin and 2,5-diOH-benzoic-acid). Specific polyphenols, such as urolithin-A and 4-ethylphenol, were directly involved with clinical weight-related changes. Conclusions: The Mankai new plant is rich in various unique potent polyphenols, potentially affecting the metabolomic-gut-clinical axis.

Highlights

  • Plants produce secondary metabolites known as polyphenols in order to defend themselves from stressors such as insect herbivores, microbial infection and UV light [1].Polyphenol bioavailability is affected by environmental factors, storage conditions and cooking methods [2]

  • 198 different phenolic metabolites were detected in all experiments, mainly from the flavonoids and phenolic acids classes

  • We found a significant correlation of the following polyphenols (6-month relative change, three intensities change annotated to two polyphenols) with the 6-month change in serum folate: hydroxy phenyl acetic acid (r = 0.136, p = 0.024) and urolithin A

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Summary

Introduction

Plants produce secondary metabolites known as polyphenols in order to defend themselves from stressors such as insect herbivores, microbial infection and UV light [1].Polyphenol bioavailability is affected by environmental factors, storage conditions and cooking methods [2]. Across ~8000 polyphenolic structures described, the main groups are classified by the number of phenol rings they contain and structural elements. Among the 100 richest dietary sources of polyphenols are cloves, cocoa powder, black olives, green tea, extra virgin olive oil, different berries, nuts and wine [4]. Due to their antioxidant property, dietary polyphenols may have a beneficial effect on human and animal health, including liver protection, anticancer activities [5], reduced cardiovascular risk [6] and reduced inflammation [7]. Several Mankai-related plasma and urine polyphenols were differentially elevated in the green Mediterranean group compared with the other groups (p < 0.05) after six and 18 months of intervention

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