The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols

• Main Authors: Anat Yaskolka Meir, Kieran Tuohy, Martin von Bergen, Rosa Krajmalnik-Brown, Uwe Heinig, Hila Zelicha, Gal Tsaban, Ehud Rinott, Alon Kaplan, Asaph Aharoni, Lydia Zeibich, Debbie Chang, Blake Dirks, Camilla Diotallevi, Panagiotis Arapitsas, Urska Vrhovsek, Uta Ceglarek, Sven-Bastiaan Haange, Ulrike Rolle-Kampczyk, Beatrice Engelmann, Miri Lapidot, Monica Colt, Qi Sun, Iris Shai
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Nutrients
• Subjects: <i>Wolffia globosa</i>; polyphenols; flavonoids; plant-based nutrition; weight loss; Mediterranean diet
• Online Access: https://www.mdpi.com/2072-6643/13/6/1866

Background: Polyphenols are secondary metabolites produced by plants to defend themselves from environmental stressors. We explored the effect of <i>Wolffia globosa</i> ‘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 (<i>p </i>< 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.