Inflammatory Bowel Disease Therapies and Gut Function in a Colitis Mouse Model

Abstract

Background. Exclusive enteral nutrition (EEN) is a well-established approach to the management of Crohn’s disease.Aim. To determine effects of EEN upon inflammation and gut barrier function in a colitis mouse model.Methods. Interleukin-10-deficient mice (IL-10−/−) were inoculated withHelicobacter trogontumand then treated with EEN, metronidazole, hydrocortisone, or EEN and metronidazole combination. Blood and tissue were collected at 2 and 4 weeks with histology, mucosal integrity, tight junction integrity, inflammation, andH. trogontumload evaluated.Results.H. trogontuminduced colitis in IL-10−/−mice with histological changes in the cecum and colon. Elevated mucosal IL-8 mRNA in infected mice was associated with intestinal barrier dysfunction indicated by decreased transepithelial electrical resistance and mRNA of tight junction proteins and increased short-circuit current, myosin light chain kinase mRNA, paracellular permeability, and tumor necrosis factor-αand myeloperoxidase plasma levels (P<0.01for all comparisons). EEN and metronidazole, but not hydrocortisone, treatments restored barrier function, maintained gut barrier integrity, and reversed inflammatory changes along with reduction ofH. trogontumload (versus infected controlsP<0.05).Conclusion.H. trogontuminfection in IL-10−/−mice induced typhlocolitis with intestinal barrier dysfunction. EEN and metronidazole, but not hydrocortisone, modulate barrier dysfunction and reversal of inflammatory changes.