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Diet and inflammatory bowel disease; a metabolomic approach

  • Author / Creator
    Hassanzadeh Keshteli, Ammar
  • Introduction:
    Inflammatory bowel disease (IBD), which is consisted of ulcerative colitis (UC) and Crohn’s disease (CD), is a relapsing-remitting inflammatory condition of gastrointestinal tract. Although the exact pathophysiology of IBD is not known yet, it has been suggested that a combination of various genetic, microbial, immunological and environmental factors play a role in IBD developments. Previous epidemiological and experimental studies have suggested that dietary factors are among the major environmental contributors of IBD development. Furthermore, many IBD patients attribute their disease onset or relapse to dietary factors. In addition, only a limited number of clinical trials have been carried out to investigate the beneficial effects of dietary modifications for management of IBD symptoms or prevention of disease relapse. However, understanding the role of diet in IBD is challenging due to its multi-faceted effects on host and microbial factors. It has recently been suggested that metabolomics which is the science of studying metabolites in different biological samples in a comprehensive way has the potential to be used for unraveling the role of diet in chronic diseases.
    Objectives: In the present thesis, our aim was to investigate the role of diet in the development or management of IBD using a metabolomic approach.
    Methods: This thesis is consisted of four sub-projects. In the first study, urinary metabolome was compared between a group of CD patients who developed CD recurrence after ileocolonic resection (n=28) and CD patients who were still in remission after ileocolonic resection (n=10). In the second study the usefulness of urinary metabolomic profiling was assessed to differentiate between UC patients (n=53) and irritable bowel syndrome (IBS) patients (n=39). In the third project which was a prospective cohort study in UC patients in clinical remission (n=20), the dietary, clinical and metabolomic factors at baseline were compared between patients who presented with UC clinical relapse during the 1-year follow-up and patients who were still in clinical remission. In the last project which was a 6-month randomized controlled trial, 53 adults UC patients were randomized to either an anti-inflammatory diet or a control diet (Canada’s Food Guide). The effects of the anti-inflammatory diet for maintenance of remission and prevention of colonic inflammation and the underlying mechanisms were assessed using a metabolomic approach.
    Results:
    Endoscopic recurrence was associated with increased concentration of urinary levoglucosan which is a diet-related metabolite. In addition, urinary metabolomic profiles of UC patients was significantly different from urinary metabolomic profiles of IBS patients. Decreased amino acids were characteristics of metabolome in UC patients. Furthermore, we found that metabolites in urine and serum could be related to clinical relapse in UC patients. Finally, we should that following an anti-inflammatory diet for 6 months could prevent increases in fecal calprotectin; a major biomarker of colonic inflammation in UC patients. We also identified a number of host and diet-related metabolites in urine and serum that significantly changed from baseline to the end of the study in patients randomized to the anti-inflammatory diet.
    Conclusions:
    These findings indicate that metabolomics can be used in IBD settings to explore the role of diet in the pathophysiology or management of the disease. These findings provide a basis for further research in this field.

  • Subjects / Keywords
  • Graduation date
    Spring 2020
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/r3-47b0-nc90
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.