Mediterranean diet, gut microbiota, and type 2 diabetes: A systematic review and meta-analysis of intervention trials

AIMS: The Mediterranean diet (MedD) is associated with improved metabolic health and modulation of gut microbiota (GM), both relevant to preventing type 2 diabetes (T2D) and cardiovascular disease (CVD). This systematic review and meta-analysis evaluated the effects of MedD-based dietary interventions on metabolic outcomes and GM composition in individuals at increased risk of T2D and CVD. DATA SYNTHESIS: We searched PubMed, Embase, Web of Science, Cochrane CENTRAL, and Scopus up to October 11, 2024, for randomized controlled trials (RCTs) comparing MedD-based diets to control diets in adults. Studies reporting outcomes on glucose metabolism and GM composition were included. Random-effects meta-analyses were conducted on metabolic outcomes. GM findings were synthesized descriptively due to heterogeneity in sequencing methods and taxonomic reporting. Nine RCTs (n = 1337 participants) met the inclusion criteria. Compared with control diets, MedD interventions significantly reduced glycated hemoglobin (HbA1c) (mean difference -0.18, 95 % CI = -0.35, -0.01), LDL cholesterol (-0.10, 95 % CI = -0.19, -0.00), and triglycerides -0.20, 95 % CI = -0.28, -0.12). No significant effects were observed on fasting glucose, insulin, HOMA-IR, total cholesterol, or HDL cholesterol. A qualitative GM analysis showed increased α-diversity and enrichment of health-related taxa, including Akkermansia muciniphila and Roseburia spp. CONCLUSIONS: Our findings suggest that MedD interventions improve HbA1c, LDL cholesterol, and triglycerides, and promote beneficial GM changes. These may contribute to the metabolic benefits of the MedD. Future research should focus on individualized approaches, longer intervention periods, and mechanistic insights using multi-omics data to better understand the diet-microbiota-host interaction. PROTOCOL REGISTRATION: PROSPERO as CRD42023428016.