The metabolomic-gut-clinical axis of mankai plant-derived dietary polyphenols

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 EngelmannMiri Lapidot, Monica Colt, Qi Sun, Iris Shai

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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. Re-sults: 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 com-pound degradation. In humans, several Mankai-related plasma and urine polyphenols were differ-entially 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-ethylphe-nol, 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-clini-cal axis.

Original languageEnglish (US)
Article number1866
Issue number6
StatePublished - Jun 2021


  • Flavonoids
  • Mediterranean diet
  • Plant-based nutrition
  • Polyphenols
  • Weight loss
  • Wolffia globosa

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics


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