Gut microbiome mediates the association between dietary quality and metabolic risk in a heterogeneous adult population

Background: Diet is a determinant of metabolic health, partly through its effects on the gut microbiome, which influences nutrient metabolism, inflammation, and energy balance. We investigated the mediating role of gut microbiome features in the association between dietary quality and metabolic risk. Methods: In this cross-sectional study, we included 269 adults aged 25–76 years with heterogeneous metabolic profiles, BMI ranging from 17.5 to 47.6 kg/m², and fasting glucose levels between 5.6 and 6.9 mmol/L. Dietary quality was assessed using the Healthy Eating Index (HEI-MON), the Planetary Health Diet Index (PHEI-MON), and the alternate Mediterranean Diet Score (aMED), derived from food-frequency questionnaires and three-day food records. Metabolic risk was quantified using a continuous metabolic syndrome score (cMetS) incorporating waist circumference, mean arterial pressure, HDL cholesterol, triglycerides, and fasting glucose. Microbiome composition (16 S rRNA gene sequencing) and predicted SCFA pathways were analyzed using adjusted multiple linear regression, PERMANOVA, and differential abundance analysis. Mediation analyses examined microbial features as potential mediators of the association between diet and metabolic risk. Results: Higher HEI-MON, PHEI-MON, and aMED were associated with lower cMetS (q < 0.01). Christensenellaceae R7 group and Ruminococcaceae NK4A214 group were enriched with higher dietary quality and lower cMetS (q < 0.1), whereas Lachnoclostridium were associated with lower diet quality and higher cMetS (q < 0.1). The Enterotype Dysbiosis Score (EDS) correlated inversely with dietary quality (PHEI-MON q = 0.04) and positively with cMetS (q = 0.04). Butyrate-synthesis pathways were more abundant in individuals with higher dietary quality (q < 0.05) and inversely associated with cMetS (q < 0.05). Mediation analysis indicated that the Ruminococcaceae NK4A214 group, the Christensenellaceae R7 group, and Lachnoclostridium accounted for up to 16% of the association between diet and metabolic risk. Conclusion: Better dietary quality is associated with lower metabolic risk and positive gut microbiome signatures across taxonomic, functional, and stability-related aspects. Certain taxa statistically mediated these associations, highlighting gut microbiome features that may contribute to observed links between dietary patterns and metabolic health.