Exclusive Enteral Nutrition (EEN) is as efficacious as corticosteroids (CS) to induce remission in Crohn's disease (CD), without their adverse effects. EEN seems to be more efficient than steroids to induce mucosal healing, but the underlying molecular mechanisms are only sparsely understood. We aimed in the present work to study the anti-inflammatory effects of EEN with Modulen IBD® versus CS in active pediatric CD and to assess its modulatory effects on the intestinal microbiota as compared to steroids. MATERIAL AND METHODS: Nineteen patients with new-onset active CD (Harvey Bradshaw index HBI> 5), aged from 6 to 17 years, were included in this prospective randomized induction trial with CS (n=6) or EEN (n=13). Patients were assessed at Week 0 and 8 using clinical parameters HBI, endoscopic findings (CDEIS score) and analysis of fecal microbiota composition. RESULTS: At 8 weeks, clinical remission (HBI<5) was achieved in 13/13 patients on EEN and 5/6 patients on steroids, while the mucosal healing rate was significantly higher in the EEN (89%) compared to steroid group (17%). There were no significant differences between groups regarding biological markers, while the intestinal microbiota profiles shifted upon EEN-induced remission to a higher proportion of Ruminococcus bacteria compared to steroid induced remission (p=0.049), with higher proportions of bacteria belonging to Clostridium in EEN-treated patients. CONCLUSION: Both steroids and EEN induced clinical remission, however, patients with EEN-induced remission showed a higher rate of mucosal healing and this was associated with a different gut microbiota compositional shift in these children. This clinical trial was registered under the number ClinicalTrials.gov Identifier: NCT00265772.