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 Engelmann,
Miri Lapidot,
Monica Colt,
Qi Sun,
Iris Shai
Affiliations
Anat Yaskolka Meir
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Kieran Tuohy
Department of Food Quality and Nutrition, Fondazione Edmund Mach, Research and Innovation Centre, Via E. Mach, 1, San Michele all’Adige, 38098 Trento, Italy
Martin von Bergen
Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbH, 04318 Leipzig, Germany
Rosa Krajmalnik-Brown
Biodesign Center for Health through Microbiomes, School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ 85281, USA
Uwe Heinig
Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
Hila Zelicha
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Gal Tsaban
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Ehud Rinott
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Alon Kaplan
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Asaph Aharoni
Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
Lydia Zeibich
Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ 85287, USA
Debbie Chang
Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ 85287, USA
Blake Dirks
Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ 85287, USA
Camilla Diotallevi
Department of Food Quality and Nutrition, Fondazione Edmund Mach, Research and Innovation Centre, Via E. Mach, 1, San Michele all’Adige, 38098 Trento, Italy
Panagiotis Arapitsas
Department of Food Quality and Nutrition, Fondazione Edmund Mach, Research and Innovation Centre, Via E. Mach, 1, San Michele all’Adige, 38098 Trento, Italy
Urska Vrhovsek
Department of Food Quality and Nutrition, Fondazione Edmund Mach, Research and Innovation Centre, Via E. Mach, 1, San Michele all’Adige, 38098 Trento, Italy
Uta Ceglarek
Institute for Laboratory Medicine, University of Leipzig Medical Center, 04103 Leipzig, Germany
Sven-Bastiaan Haange
Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbH, 04318 Leipzig, Germany
Ulrike Rolle-Kampczyk
Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbH, 04318 Leipzig, Germany
Beatrice Engelmann
Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbH, 04318 Leipzig, Germany
Miri Lapidot
Research and Development Department, Hinoman Ltd., Rishon Lezion 7546302, Israel
Monica Colt
Research and Development Department, Hinoman Ltd., Rishon Lezion 7546302, Israel
Qi Sun
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
Iris Shai
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
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.