| Summary: | The approach to studying diet–health relationships has progressively shifted from
individual dietary components to overall dietary patterns that affect the interaction and balance of
low-molecular-weight metabolites (metabolome) and host-enteric microbial ecology (microbiome).
Even though the Mediterranean diet (MedDiet) has been recognized as a powerful strategy to
improve health, the accurate assessment of exposure to the MedDiet has been a major challenge in
epidemiological and clinical studies. Interestingly, while the effects of individual dietary components
on the metabolome have been described, studies investigating metabolomic profiles in response
to overall dietary patterns (including the MedDiet), although limited, have been gaining attention.
Similarly, the beneficial effects of the MedDiet on cardiometabolic outcomes may be mediated through
gut microbial changes. Accumulating evidence linking food ingestion and enteric microbiome
alterations merits the evaluation of the microbiome-mediated effects of the MedDiet on metabolic
pathways implicated in disease. In this narrative review, we aimed to summarize the current
evidence from observational and clinical trials involving the MedDiet by (1) assessing changes in the
metabolome and microbiome for the measurement of diet pattern adherence and (2) assessing health
outcomes related to the MedDiet through alterations to human metabolomics and/or the microbiome.
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