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The metabolomic-gut-clinical axis of Mankai plant-derived dietary polyphenols.

Yaskolka, M.A., K. Tuohy K, M. von Bergen, R. Krajmalnik-Brown, U. Heinig, H. Zelicha, G. Tsaban, E. Rinott, A. Kaplan, A. Aharoni, L. Zeibich, D. Chang, B. Dirks, C. Diotallevi, P. Arapitsas, U. Vrhovsek, U. Ceglarek, S.-B. Haange, U. Rolle-Kampczyk, B. Engelmann, M. Lapidot, M. Colt, Q. Sun, I., 2021. The metabolomic-gut-clinical axis of Mankai plant-derived dietary polyphenols. Nutrients. 13(6):1866.

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.