A Microbiota-Targeted Mediterranean Diet-Based Intervention (IBDMED) to Reduce Post-Operative Recurrence in Patients with Crohn’s Disease: A Pilot Randomized Controlled Trial

Background and aims Post-operative recurrence in Crohn’s disease (CD) remains common despite advances in biologic therapies. Gut microbiota dysbiosis plays a key role in recurrence, highlighting the need for complementary, microbiota-targeted strategies. The IBDMED program--an adapted Mediterranean diet designed to modulate the microbiome--has shown promise in reducing inflammation and promoting a favourable microbial profile. We propose a pilot randomized controlled trial to evaluate the feasibility and preliminary effects of the IBDMED intervention in patients with CD following intestinal resection. Forty consecutive patients will be randomized to standard of care (SOC) alone or SOC in addition to the IBDMED intervention, which includes structured nutritional counselling, a digital support platform, and weekly follow-up with dietitians. The intervention begins four weeks post-operatively and is individually adapted based on symptoms, nutritional status, and food tolerance. The primary objective is to assess the feasibility and acceptability of the intervention, including adherence (IBDMED score). Secondary outcomes include clinical activity (CDAI, HBI), inflammatory markers (fecal calprotectin, CRP), quality of life (PRO-2/3, SIBDQ), intestinal ultrasound at 3- and 6- months post-operatively, and endoscopic recurrence (Rutgeerts score at 6-9 months). Methods Exploratory analyses will assess changes in gut microbiota and fecal metabolites using metagenomics and targeted metabolomics, respectively. Anticipated impact Findings from this pilot study will inform the feasibility and design of a larger, definitive trial assessing the efficacy of microbiota-targeted dietary strategies to reduce post-operative recurrence and improve long-term outcomes in CD. If successful, the IBDMED intervention could be integrated into standard care as a non-pharmacological and scalable strategy that may modify disease risk of post-operative recurrence, improve quality of life and reduce unnecessary long-term dietary restrictions.