Mechanistic Implications of the Mediterranean Diet in Patients With Newly Diagnosed Crohn's Disease: Multiomic Results From a Prospective Cohort

Background & Aims: To decipher the mechanisms underlying the protective role of the Mediterranean diet (MED) in Crohn's disease (CD), we explored the implications of adherence to MED on CD course, inflammatory markers, and microbial and metabolite composition. Methods: Patients with newly diagnosed CD were recruited and followed prospectively. MED adherence was assessed by repeated food frequency questionnaires (FFQs) using a predefined inflammatory bowel disease Mediterranean diet score (IBDMED score), alongside validated MED adherence screeners. Crohn's disease activity index (CDAI), C-reactive protein, fecal calprotectin, and microbial composition (16S-ribosomal RNA sequencing) were assessed each visit. Baseline serum and fecal samples were analyzed for targeted quantitative metabolomics. Results: Consecutive patients: 271 (52% men, average age 31 ± 12 years, B1 phenotype 75%). FFQs collected: 636 (range 1–5 FFQs per patient). Adherence to MED was associated with a noncomplicated CD course, and inversely correlated with CDAI, fecal calprotectin, C-reactive protein, and microbial dysbiosis index (all P < .05). Increasing adherence to MED over time correlated with reduced CDAI and inflammatory markers (P < .05). Adherence to MED correlated with a microbial cluster of commensals and short-chain fatty acid producers including Faecalibacterium, and with plant metabolites, vitamin derivatives, and amino acids. Conversely, adherence to MED inversely correlated with a cluster of oral genera, Escherichia coli and Ruminococcus gnavus, known CD-associated species, and with tryptophan metabolites, ceramides, and primary bile acids (false discovery rate < 0.2). Conclusion: Adherence to MED is associated with beneficial clinical outcomes and decreased inflammatory markers. These may be driven by lower levels of primary bile acids and microbial dysbiosis and a beneficial microbial and metabolite composition. Randomized controlled trials are needed to evaluate the role of MED in CD management.