OBJECTIVES: Exclusive enteral nutrition (EEN) is the first-line treatment for pediatric Crohn's disease, but its mechanisms of action remain poorly understood. Our aim was to identify the mechanisms that could explain the anti-inflammatory effects of EEN, studying the nutritional composition and transforming growth factor-β (TGF-β) effects, in a mouse model of colitis. METHODS: Mice were treated with dextran sulfate sodium (DSS) to induce colitis. After DSS treatment, we compared two enteral nutrition formulas, and we evaluated the effect of TGF-β itself on clinical and microscopic inflammation, and intestinal permeability, by TGF-β-supplementation, -inhibition, or -deletion. Colonic crypts from DSS and EEN mice were cultured and their cellular properties were analyzed. RESULTS: Both EEN formulas improved weight recovery and disease activity index. In contrast, EEN mice treated with TGF-β formula presented faster weight recovery and decreased inflammatory parameters, with a normalized intestinal permeability, suggesting gut restitution and functionality. These functional improvements were not found in the absence of TGF-β in the formulas. Finally, organoids from colonic crypts treated with Modulen IBD® containing TGF-β showed enhanced survival and re-epithelialization capacity. CONCLUSIONS: Both EEN formulas have anti-inflammatory properties based on their nutritional composition. However, TGF-β plays a significant role in intestinal functional restitution.
Boumessid et al. (Tue,) studied this question.