title: Dietary Non-digestible Polysaccharides Ameliorate Intestinal Epithelial Barrier Dysfunction in IL-10 Knockout Mice.
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.
authors.affiliation: Department of General Surgery, Taizhou People's Hospital, Medical School of Nantong University, Taizhou, China Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Model Animal Research Center of Nanjing University, Nanjing, China.
authors.forename: Peiliang
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Lugen
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Taizhou People's Hospital, Medical School of Nantong University, Taizhou, China drliuqinghong@126.com.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D003092:Colitis / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D004043:Dietary Fiber / Q000627:therapeutic use*; D004750:Enteral Nutrition / Q000379:methods*; D016753:Interleukin-10 / Q000172:deficiency*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D011134:Polysaccharides / Q000627:therapeutic use*; D056692:Prebiotics; D012720:Severity of Illness Index; D019108:Tight Junctions / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004043:Dietary Fiber; D011134:Polysaccharides; D056692:Prebiotics; D016753:Interleukin-10
keywords: IL-10 knockout; Multi-fibre mix; apoptosis; barrier function; regulatory T cells; short chain fatty acids; tight junction