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Non-digestible fibers and dietary interventions: alternative approaches for the treatment of inflammatory bowel disease

  • Author / Creator
    Koleva, Petya T
  • Crohn’s disease (CD) and ulcerative colitis (UC), collectively called inflammatory bowel disease (IBD), are associated with chronic intestinal inflammation, affecting approximately 0.7 % of Canadians. Intestinal microbial dysbiosis have been related to IBD. Therapies that manipulate gut microbiota including interventions with non-digestible fermentable carbohydrates, present a promising treatment. This thesis aimed to test the hypotheses: non-digestible fermentable fibers prevent colitis development in experimental and human IBD, and bacterial fermentation products, mucosal integrity and gut associated lymphoid tissue may control microbiota of the host. The anti-inflammatory properties of β-fructans mixture, fructo-oligosaccharides (FOS) plus inulin, were verified in a clinical trial with patients with mild to moderate active UC. Patients received 7.5 g or 15 g daily oral β-fructans for 9 weeks. Improvements in UC patients treated with beta-fructans were associated with shifts in the composition of intestinal microbiota and improved butyrate formation. The effects of the short-chain FOS versus the long-chain inulin were compared in an animal study of IBD, using HLA-B27 transgenic rats. The results demonstrated that FOS and inulin differ in colitis reduction and also vary in their effects on the intestinal microbiota in HLA-B27 transgenic rats. The protective effects of FOS in this animal model were associated with an increased abundance of bifidobacteria in intestinal microbiota. A second animal study aimed to compare FOS and isomalto-oligosaccharides, with different structure, in combination with two different diets on inflammation and intestinal microbiota composition in experimental IBD. The protective effects of fibers on colitis development depended on the diet background. The specific cecal microbiota changes were not associated with colitis reduction. Inflammation was positively correlated to protein fermentation in the colon but was negatively associated with carbohydrate fermentation. The last study aimed to investigate if dysregulated mechanisms of intestinal epithelial barrier in IBD may contribute to microbial dysbiosis. Expression of genes, involved in barrier function, was studied in samples obtained from UC and CD patients. Gene expression of mucins and anti-microbial peptides was associated with IBD disease type and these findings confirm and extend previous work that epithelial barrier dysfunction may contribute to microbiota dysbiosis in IBD.

  • Subjects / Keywords
  • Graduation date
    2014-06
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R33776245
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Agricultural, Food, and Nutritional Science
  • Specialization
    • Nutrition and metabolism
  • Supervisor / co-supervisor and their department(s)
    • Dieleman, Levinus (Department of Medicine)
    • Gaenzle, Michael (Department of Agricultural, Food, and Nutritional Science)
  • Examining committee members and their departments
    • Dieleman, Levinus (Department of Medicine)
    • Willing, Benjamin (Department of Agricultural, Food, and Nutritional Science)
    • Gaenzle, Michael (Department of Agricultural, Food, and Nutritional Science)
    • Reid, Gregor (Western University, London, Ontario)
    • Madsen, Karen (Department of Medicine)