Abstract
Background Clinical data suggest that enteral nutrition (EN) effectively decreases disease activity and maintains remission in patients with inflammatory bowel disease (IBD). However, the modulatory effects of EN on the intestinal mucosal immune system remain unclear. Aims This study first aimed at comparing the therapeutic effects of three EN formulas on ameliorating dextran sulfate sodium- (DSS-) induced chronic colitis; with the most effective formula, we then examined its influence on the mucosal inflammatory response and epithelial barrier function. Methods The effect of EN formulas on colitis in mice was assessed by body weight, disease activity index scores, colon length, and H&E staining for pathological examination. Colonic and circulating cytokine expression levels and the frequencies of immune cells were also analyzed. Intestinal epithelial barrier function was evaluated by detecting tight junction proteins. Results We found that among the three EN formulas, an elemental diet (ED) containing enriched amino acids restored the colitis-related reduction in body weight better than the other two EN formulas. ED amino acids suppressed the release of colonic proinflammatory mediators and maintained the expression of tight junction proteins in these mice. ED amino acid treatment mitigated the colitis-induced increase in CD103+CD11b+ dendritic cells and CD4+ and CD8+ T cells and inhibited the predominant Th1/Th17 responses particularly in the colonic mucosal lamina propria of mice with colitis. Conclusions We showed that ED amino acids can be an effective immunomodulatory agent to reduce colitis-related inflammation by inhibiting proinflammatory mediators and Th1/Th17 cell responses and by repairing the disrupted epithelial barrier.
Highlights
Nutritional disturbances represent a frequent manifestation in inflammatory bowel disease (IBD) patients, especially those with Crohn’s disease (CD) [1]
We aimed to examine whether these three enteral nutrition (EN) formulas could ameliorate disease activity in mice with chronic colitis induced by dextran sulfate sodium (DSS) and to compare their therapeutic efficacy
The three different ENs resulted in the obvious suppression of colitis severity, including significant reversals in body weight loss and colon length reduction, reduced Disease activity index (DAI) scores, and decreased lymphocytic infiltration in the colon (Figures 1(a)–1(d))
Summary
Nutritional disturbances represent a frequent manifestation in inflammatory bowel disease (IBD) patients, especially those with Crohn’s disease (CD) [1]. EN remains of interest for patients presenting with malnutrition, those who failed with other therapeutics, patients with complications, or selected patients on long-term maintenance therapy with fewer side effects [3,4,5] It has been used as a first-line therapy for pediatric patients with CD [6] and was shown to induce clinical remission and mucosal healing and improve body composition in patients with CD [7,8,9]. These data suggested that EN effectively decreases disease activity and maintains remission in patients with IBD, but the potential mechanism is multifactorial, generally due to its anti-inflammatory effects and regulation of the intestinal. We showed that ED amino acids can be an effective immunomodulatory agent to reduce colitis-related inflammation by inhibiting proinflammatory mediators and Th1/Th17 cell responses and by repairing the disrupted epithelial barrier
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