Journal Article Ahead of print
PubMed: 42478557 DOI: 10.1002/jpn3.70517
Exclusive enteral nutrition containing transforming growth factor-β improves intestinal barrier function in a colitis mouse model.
J Pediatr Gastroenterol Nutr
Authors: Kawthar Boumessid, Vickie Lacroix, Ekaterina Ovtchinnikova, Sophie Thenet, Marie Carriere, Frédérick Barreau, Emmanuel Mas
Affiliations
- INSERM UMR1220, INRAE, ENVT, University of Toulouse, Toulouse, France.
- INSERM UMR1220, INRAE, ENVT, University of Toulouse, Toulouse, France. Gastroenterology, Hepatology, Nutrition, Diabetes and Inborn Errors of Metabolism Department, Children Hospital, Toulouse University Hospital, Toulouse, France.
- UMR 938, Research Center of Saint-Antoine, Sorbonne University, INSERM, Paris, France.
- EPHE, PSL University, Paris, France.
- SyMMES, University of Grenoble, CEA, INP, CNRS, Grenoble, France.
- Gastroenterology, Hepatology, Nutrition, Diabetes and Inborn Errors of Metabolism Department, Children Hospital, Toulouse University Hospital, Toulouse, France.
Abstract
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.
MeSH
Growth, Colitis, Transforming Growth Factors, Recycling, Therapeutics, Enteral Nutrition