Gut microbiome profiles and associated functional pathways are linked to Mediterranean diet adherence and blood glucose control in adults with type 1 diabetes mellitus

1. Background and Aims The Mediterranean diet (MD) has been associated with better glycaemic control in children with type 1 diabetes mellitus (T1DM) and favourable microbiome profiles in healthy individuals. However, it remains unclear whether MD adherence is associated with glycaemic control via microbiome. This study examined the relationships among MD adherence, gut microbiome, and glycaemic control in adults with T1DM and assessed the microbiome’s ability to predict clinical and dietary outcomes. 2. Methods and Results In a cross-sectional study of 253 adults with T1DM, dietary intake was assessed using the EPIC food frequency questionnaire, and MD adherence was measured using the rMED score. Participants were stratified by adherence level (low, medium, high). Glycaemic control was evaluated using HbA1c and CGM metrics. Shotgun metagenomic sequencing of stool samples (n=103) assessed the gut microbiome. Statistical analyses included ANOVA, PERMANOVA, LEfSe, and machine learning modeling. Higher MD adherence was associated with lower HbA1c levels (7.1% vs 7.7%; p<0.001), greater time in range (67.0% vs 59.4%; p-trend=0.03), and higher HDL cholesterol (1.62 vs 1.39 mmol/L; p=0.01). High MD adherence was linked to a greater abundance of bacterial species such as Faecalibacterium prausnitzii. Both high MD adherence and lower HbA1c were associated with distinct microbiome functional pathways. Microbiome-based machine learning models predicted dietary patterns and clinical metrics. 3. Conclusions In adults with T1DM, greater MD adherence is associated with better glycaemic control and a favourable gut microbiome. Specific microbial pathways may underlie these associations. Integrating diet and microbiome data supports personalized care. The study was registered at ClinicalTrials.gov with the identifier NCT05936242.