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The Mediterranean Diet (MedDiet) is known to decrease the cardiometabolic risk through modulation of metabolic pathways. However, the interplay between MedDiet, metabolites and microbial metabolism is not yet fully understood. A new crossover randomized clinical trial aimed to evaluate the effect of the MedDiet compared to nuts supplementation on circulating metabolites and their relationship with cardiometabolic health, and examine whether changes in the metabolomic profiles were associated with changes in gut microbiota composition. Findings showed that changes in 65 circulating metabolites were significantly associated with the MedDiet (mainly lipids, acylcarnitines, amino acids, steroids and tricarboxylic acid intermediates). Importantly, these changes were associated with decreases in glucose, insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Two main clusters of bacteria were also identified, with an opposite behaviour towards selected metabolites. Therefore, following a MedDiet, rather than consuming nuts in the context of a non-MedDiet, was associated with a specific plasma metabolomic profile, which was also related to metabolic improvements in adults with metabolic syndrome (MetS). The identified correlated network between specific bacteria and metabolites suggests interplay between diet, circulating metabolites and gut microbiota.
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