Dietary Non-digestible Polysaccharides Ameliorate Intestinal Epithelial Barrier Dysfunction in IL-10 Knockout Mice

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Abstract

Background:

Enteral nutrition [EN] was reported to be as effective as steroids in achieving short-term remission in patients with Crohn’s disease [CD], and exclusive EN [EEN] is widely used as primary therapy in children with CD. The aim of this study was to investigate the effect of a specific multi-fibre mix [MF], designed to match the fibre content of a healthy diet, on intestinal epithelial barrier function in IL-10 knockout [IL-10−/−] mice with spontaneous chronic colitis.

Methods:

IL-10−/− mice aged 16 weeks, with established colitis, were used for the experiments with multi-fibre mix diet [MF] for 4 weeks. Severity of colitis, levels of short cahin fatty acids [SCFA] in caecum contents, expression of STAT 3 and STAT 4 proteins, CD4+ CD45+ lymphocytes, CD4+Foxp3+ regulatory T cells [Tregs] and cytokines in the lamina propria [LP], epithelial expression of tight junction proteins, TNF-α/TNFR2 mRNA expression, and epithelial apoptosis in the proximal colon were measured at the end of the experiment.

Results:

MF feeding effectively attenuated disease activity index and colitis associated with decreased lamina propria CD4+ CD45+ lymphocytes, IFN-γ/IL-17A mRNA expression, and p-STAT 3 and p-STAT 4 expression in colonic mucosa of IL-10−/− mice [p < 0.05]. Furthermore, CD4+Foxp3+ Tregs in the LP and concentrations of total SCFA, acetate, propionate, and butyrate in the caecum were markedly increased after MF feeding in IL-10−/− mice. After MF feeding, increased epithelial expression and correct localisation of tight junction proteins [occludin and zona occludens protein 1], as well as reduced TNF-α/TNFR2 mRNA expression and epithelial apoptosis, were also observed in IL-10−/− mice.

Conclusions:

These results indicated that EEN supplemented with the tested fibre mix, known to modulate the intestinal microbiota composition and SCFA production, could possibly improve efficacy in inducing remission in patients with active CD.

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