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The green Mediterranean diet (MED) has a striking effect on the microbial population of the human gut (i.e., the “gut microbiome"). In a large-scale clinical interventional trial- the DIRECT PLUS - the gut microbiome of green MED dieters was enriched with bacteria that are known to have a significant effect on human weight and glycemic control. A novel analysis revealed that the health-promoting effects, previously attributed to the green MED diet, are in fact mediated by the changes in the gut microbiome.



The study was published today in Genome Medicine, a leading international journal focused on translational, genomic-based medicine.



The research was led by Prof. Iris Shai (pictured below), director of The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, and an adjunct professor in the Harvard School of Public Health, together with her MD-PhD student Dr. Ehud Rinott, Prof. Ilan Youngster from Shamir Medical Center and Tel-Aviv University, and several selected international experts.



The DIRECT-PLUS trial research team, led by Prof. Shai, was the first to introduce the concept of the green-Mediterranean diet. This modified MED diet is further enriched with dietary polyphenols and lower in red/processed meat than the traditional healthy MED diet. On top of a daily intake of walnuts (28 grams), the participants consumed 3-4 cups of green tea/day and 100 grams (frozen cubes) of duckweed green shake/day. The aquatic green plant duckweed is high in bioavailable protein, iron, B12, vitamins, minerals, and polyphenols and substituted meat intake.



The novel findings may explain the previously published green-MED diet effects noted in the DIRECT PLUS trial, that a high-polyphenol, green plant-based diet better optimizes the microbiome for autologous fecal microbiota transplantation (aFMT) procedure, that green-MED diet can amplify the remission of fatty liver, improve LDL cholesterol, glycemic control, CRP and blood pressure control and attenuate age-related brain atrophy, as compared to the traditional, healthy MED diet.



The results showed that while all diets induce substantial changes to the gut microbiome community, the changes of green-MED dieters are much more pronounced. Interestingly, the beneficial changes in the gut of green MED dieters were attributed to the tendency of this novel diet to specifically affect the rare bacteria in the subjects' intestines. This phenomenon was possibly due to the fact that the prominent component of the diet, duckweed, is¬ new to the Western palate, allowing usually concealed microbes to flourish under the new gut environment induced by the plant.



The green MED diet induced specific microbial changes, including enrichments in the genus Prevotella, a bacteria known for its positive effects on glucose metabolism and insulin sensitivity, while also promoting genetic pathways involved in the reduction of branched-chain amino acids, compounds that are well linked to insulin resistance. Lastly, the researchers were able to show that by modifying specific gut microbes through dieting, the gut microbiome constitutes a valuable mediator between the green dietary pattern, and its effects on weight loss and reduced cardiac risk.



"These findings may strengthen our understanding regarding the significant cross-talk between our nutritional intake, the microbiome and clinical outcomes," says Prof. Shai.



“We aimed to discover how the green MED diet affects the health of its consumers. The favorable clinical results were substantial," says Dr. Ehud Rinott, first author and member of the BGU School of Public Health. “We hope that by unraveling the role of the gut microbiome in the diet's effect, we can further improve and personalize diets in the future."



"These results are another example illuminating the central role of our gut microbiome in health and disease and will further our understanding in this intriguing field", says Prof. Ilan Youngster.



This work was funded by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project number 209933838; the Rosetrees trust (grant A2623); Israel Ministry of Health grant 87472511; Israel Ministry of Science and Technology grant 3-13604; California Walnuts Commission and partially (financially) supported by the European Commission JPI-HDHL, ERA-NET project (grant agreement n.696300), CABALA_diet&health (MIPAAF Decree n. 31965/7303/16 of 29/12/2016.



None of the funding providers was involved in any stage of the design, conduct, or analysis of the study and they had no access to the study results before publication.



Prof. Ilan Youngster is an advisor for Mybiotics Ltd., Prof. Dan Knights serves as Senior Scientific Advisor to Diversigen, Inc