Novel Insights Into The Mechanisms Of Post-Infectious Irritable Bowel Syndrome Using Experimental Giardiasis
| atmire.migration.oldid | 2309 | |
| dc.contributor.advisor | Buret, Andre G. | |
| dc.contributor.advisor | Gargala, Gilles | |
| dc.contributor.author | Halliez, Marie, C.M. | |
| dc.date.accessioned | 2014-07-11T18:13:58Z | |
| dc.date.available | 2014-11-17T08:00:36Z | |
| dc.date.issued | 2014-07-11 | |
| dc.date.submitted | 2014 | en |
| dc.description.abstract | Irritable Bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder in humans characterized by abdominal pain and altered bowel habits. The major pathophysiological features of IBS include: visceral hypersensitivity, intestinal barrier dysfunction, low grade inflammation appear following acute gastroenteritis despite the clearance of the inciting pathogen. This post-infectious (PI)-IBS may occur in patients following infection with bacteria such as C. jejuni, E. coli, Salmonella spp. Recent studies have implicated protozoan parasites such as Giardia duodenalis in the appearance of PI-IBS. G. duodenalis, the most common enteropathogen worldwide, is responsible for giardiasis, a disease causing intestinal malabsorption and diarrhea in a wide variety of species including humans. Using in vivo and in vitro models, the present study, established a proof-of-concept between Giardia-infection and the development of PI-IBS. This study also characterized one of the contributing mechanisms leading to post-giardiasis IBS. In a new neonatal immunocompetent rat model, the human assemblages of Giardia duodenalis caused a significant visceral hypersensitivity 50 days post-infection in two parts of the gastrointestinal tract. Visceral hypersensitivity was associated with mucosal structure modifications: villus atrophy and crypt hyperplasia after clearance of the pathogen. It was also associated with activation of the mucosal immune system as shown by an increase in intraepithelial lymphocytes and mast cell counts during the post-infectious stage. And with activation of the nociceptive signaling pathway by induction of c-fos expression starting at day 7 post-infection and continuing until the post-infectious stage. This study showed a dysfunction of the intestinal barrier, in vivo and in vitro, characterized by the translocation of commensal bacteria. Giardia-induced bacterial translocation, further characterized in vitro, was shown to occur via the paracellular route in conjunction with the degradation of the tight junctional proteins occludin and claudin-4. In conclusion, this study presented a new animal model of giardiasis eliciting PI-IBS symptoms. This study also showed that Giardia was able to induce the translocation of commensal bacteria through the epithelial monolayer via the paracellular route by degrading tight junctional proteins. This model suggest that the host immune system reactivity toward its own microbiota due to impaired intestinal barrier function seems to be one of the mechanisms contributing to post-infectious irritable bowel syndrome following acute giardiasis. | en_US |
| dc.identifier.citation | Halliez, M. (2014). Novel Insights Into The Mechanisms Of Post-Infectious Irritable Bowel Syndrome Using Experimental Giardiasis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27133 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/27133 | |
| dc.identifier.uri | http://hdl.handle.net/11023/1627 | |
| dc.language.iso | eng | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | Parasitology | |
| dc.subject.classification | Giardia | en_US |
| dc.subject.classification | post-infectious irritable bowel syndrome | en_US |
| dc.subject.classification | hypersensitivity | en_US |
| dc.subject.classification | bacterial translocation | en_US |
| dc.subject.classification | c-Fos | en_US |
| dc.subject.classification | permeability | en_US |
| dc.subject.classification | Tight junctions | en_US |
| dc.title | Novel Insights Into The Mechanisms Of Post-Infectious Irritable Bowel Syndrome Using Experimental Giardiasis | |
| dc.type | doctoral thesis | |
| thesis.degree.discipline | Biological Sciences | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Doctor of Philosophy (PhD) | |
| ucalgary.item.requestcopy | true |