The Microbiology and Immunology of Ileocecal Resection

  • Author / Creator
  • Ileocolic resection is frequently performed for Crohn's disease; however, disease commonly recurs early in the neo-terminal ileum. The aim of this thesis was to investigate the microbial and immunologic factors inherent to ileocecal resection as they pertain to post-operative recurrence of Crohn’s disease in the ileum using mouse models.
    The ileocolic procedure was developed in the mouse and used in models of intestinal inflammation including the IL-10-/- genetic knockout and the dextran sodium sulfate induced colitis models. A multitude of techniques in cell biology and biochemistry were used to characterize the local intestinal and systemic changes in the host microbiome and immune function.

    Main results included local immune suppression in the intestinal tissues following ileocecal resection. This was associated with changes in macrophage and dendritic cell populations. Bacterial overgrowth in the ileum was found in both models of disease with with bacterial invasion into the lamina propria contributing to post-operative ileitis in the IL-10-/- mice. Significant perturbations in microbial clades defined by whole metagenome shotgun sequencing were also found.

    Ileocecal resection causes significant shifts in the both the gut microbiome and mononuclear phagocyte populations. This thesis suggests immune dysfunction with impaired microbial clearance may be to blame for the early ulcerations frequently found in the ileum of Crohn’s disease patients following ileocecal resection.

  • Subjects / Keywords
  • Graduation date
    Spring 2015
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • 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
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Specialization
    • Experimental Surgery
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Fedorak, Richard (Medicine)
    • Dicken, Bryan (Surgery)
    • Madsen, Karen (Medicine)
    • Beck, Paul (Medicine)
    • Churchill, Thomas (Surgery)