Advanced clinical applications of the Crohn's disease exclusion diet Unraveling mechanisms, identifying biomarkers and optimizing personalized therapy

Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by relapsing and remitting inflammation of the gastrointestinal tract. While its pathogenesis is multifactorial, involving genetic, immune, microbial, and environmental factors, diet has emerged as a key modifiable contributor. Exclusive enteral nutrition (EEN) is the established first-line therapy for induction of remission in children, yet its restrictive nature limits long-term feasibility. To address this, the Crohn’s Disease Exclusion Diet (CDED) was developed to replicate the benefits of EEN while offering a more palatable and sustainable approach.
This thesis is divided into two parts. Part I evaluates the clinical efficacy of CDED in both children and adults through randomized controlled trials. Findings demonstrate that CDED, with or without partial enteral nutrition (PEN), achieves high rates of clinical remission and inflammatory marker reduction, with superior tolerability compared to EEN. Notably, CDED was more effective in maintaining remission at week 12 and showed promising results in adult patients, including mucosal healing in a subset.
Part II investigates mechanisms underlying dietary therapy, focusing on the gut microbiome, intestinal permeability, and tryptophan metabolism. Sustained remission was associated with reproducible microbial shifts toward a health-associated profile, improvements in barrier function, and alterations in tryptophan-derived metabolites. Ratios of kynurenine- and serotonin-pathway metabolites emerged as potential biomarkers of treatment response.
Together, these findings establish CDED as an evidence-based dietary therapy for CD, highlight its role in sustained remission, and provide translational insights that may guide the development of predictive biomarkers and personalized nutrition strategies in IBD.