The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial.

Ehud Rinott, Anat Yaskolka Meir, Gal Tsaban, Hila Zelicha, Alon Kaplan, Dan Knights, Kieran Tuohy, Matthias Uwe Scholz, Omry Koren, Meir J Stampfer, Dong D Wang, Iris Shai, Ilan Youngster

Journal: Genome medicine 2022;14(1):29

PMID: 35264213

Plain Language Summary

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The Mediterranean (MED) diet, high in nuts, vegetables, and legumes and low in red meat intake, is recommended for the prevention of cardiometabolic diseases. It has been reported that adherence to MED dietary patterns is associated with a distinct gut microbiome profile. The main aim of this study was to investigate the effect of MED-based dietary interventions on the gut microbiome composition and function. This study was focused on the analysis of the DIRECT-PLUS trials’ secondary outcomes, including gut microbiome profile, lipid profile, glycaemic control, inflammatory state, and cardiometabolic risk. All eligible participants were randomised in a 1:1:1 ratio, into one of the three intervention groups: healthy dietary guidelines (HDG), MED, and Green-MED, all combined with physical activity accommodation. Results showed that: - the Green-MED diet [an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake] induced a prominent change in the gut microbiome composition, driven by the low-prevalent “non-core” fraction of the gut microbiome. - the MED and Green-MED diets improved cardiometabolic markers. These beneficial changes in levels of cardiometabolic biomarkers were associated with a concurrent shift in the gut microbiome composition. Authors conclude that the Green-MED diet has extensive effects on the composition and function of the host gut microbiome, with the latter partially mediating the beneficial effects of the diet on cardiometabolic health.

Abstract

BACKGROUND

Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial.

METHODS

In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples.

RESULTS

Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, "non-core," microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-MED and body weight and cardiometabolic risk reduction.

CONCLUSIONS

Our findings support a mediating role of the gut microbiome in the beneficial effects of the Green-MED diet enriched with Mankai and green tea on cardiometabolic risk factors.

TRIAL REGISTRATION

The study was registered on ClinicalTrial.gov ( NCT03020186 ) on January 13, 2017.

© 2022. The Author(s).

Address: Faculty of Health Sciences, Ben-Gurion University of the Negev, 84105, Beer-Sheva, Israel.; BioTechnology Institute, University of Minnesota, Saint Paul, MN, 55108, USA.; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.; Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, San Michele all'Adige, 38016, Trento, Italy.; University of Leeds, School of Food Science and Nutrition, Leeds, LS2 9JT, UK.; Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, San Michele all'Adige, 38016, Trento, Italy.; Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Harvard T.H. Chan School of Public Health, Boston, USA.; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. [email protected].; Pediatric Division and Center for Microbiome Research, Shamir Medical Center, Be'er Ya'akov, Israel. [email protected].; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. [email protected].; Pediatric Infectious Diseases Unit and the Center for Microbiome Research, Shamir Medical Center, 70300, Zerifin, Israel. [email protected].
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