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Permanent link (DOI): https://doi.org/10.7939/R3GT5FP8K

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The Microbiology and Immunology of Ileocecal Resection Open Access

Descriptions

Other title
Subject/Keyword
Crohn's Disease
Mucosal Immunology
Microbiome
ileocecal resection
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Perry,Troy
Supervisor and department
Dicken, Bryan (Surgery)
Madsen, Karen (Medicine)
Examining committee member and department
Dicken, Bryan (Surgery)
Churchill, Thomas (Surgery)
Fedorak, Richard (Medicine)
Beck, Paul (Medicine)
Madsen, Karen (Medicine)
Department
Department of Surgery
Specialization
Experimental Surgery
Date accepted
2015-04-02T10:37:11Z
Graduation date
2015-06
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
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.
Language
English
DOI
doi:10.7939/R3GT5FP8K
Rights
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.
Citation for previous publication
Perry, T., Borowiec, A., Dicken, B., Fedorak, R., Madsen, K. Murine Ileocolic Bowel Resection with Primary Anastomosis. J. Vis. Exp, e52106, doi:10.3791/52106 (2014).

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