Effects of the Mediterranean Diet on Gut Microbiota Composition and Diversity in Overweight and Obesity: A Scoping Review of Randomized Controlled Trials

Background: The Mediterranean diet (MedDiet) is widely associated with anti-inflammatory and metabolic benefits, and gut microbiota modulation has been proposed as a critical mechanistic pathway. However, evidence from randomized controlled trials (RCTs) remains fragmented, and it is unclear whether MedDiet produces consistent microbiome changes in overweight and obese populations. Objective: To systematically map and synthesize evidence from RCTs evaluating the effects of MedDiet interventions on gut microbiota composition, inflammatory biomarkers, and metabolic outcomes in adults with overweight or obesity. Methods: A scoping review was conducted following PRISMA-ScR guidelines. PubMed, Embase, and Scopus were searched through May 2025 for RCTs evaluating MedDiet interventions in adults with BMI ≥ 25 kg/m2 without the use of microbiota-targeted supplementation. Primary outcomes included gut microbiota composition and diversity. Secondary outcomes included inflammatory biomarkers (CRP, IL-6, TNF-α) and anthropometric or metabolic measures. Risk of bias was assessed using the RoB 2 tool. Results: Eight RCTs met inclusion criteria, of which four evaluated gut microbiota directly. MedDiet interventions were associated with selective enrichment of metabolically favorable taxa, including short-chain-fatty-acid–producing genera such as Roseburia, Faecalibacterium, and Akkermansia, supporting biologically plausible pathways linking diet to metabolic and inflammatory regulation. However, global diversity metrics—including alpha diversity and Firmicutes/Bacteroidetes ratio—showed inconsistent or non-significant changes across studies. Improvements in inflammatory markers and anthropometric outcomes were more consistently observed than microbiota diversity shifts. Notably, comparator diets—including low-fat, ketogenic, and low-carbohydrate regimens—also produced microbiome changes, highlighting the difficulty in isolating MedDiet-specific microbial effects. Substantial heterogeneity in intervention design, duration, microbiome analysis methods, and outcome prioritization limited cross-trial comparability. Conclusion: Evidence from randomized trials suggests that the Mediterranean diet may exert metabolically relevant effects through selective modulation of specific microbial taxa rather than uniform changes in global microbiome diversity. While inflammatory and metabolic improvements are consistently observed, microbiota-mediated mechanisms remain incompletely characterized. Future RCTs should incorporate standardized microbiome endpoints, longer follow-up, and mechanistic analyses to clarify causal pathways and distinguish MedDiet-specific effects from broader dietary influences.