Butyrate Alleviates Crohn's Diseases' Adherent Invasive E coli-Induced Mitochondrial Dysfunction in Intestinal Epithelium
| dc.contributor.advisor | McKay, Derek | |
| dc.contributor.author | Hamed, Samira | |
| dc.contributor.committeemember | Shutt, Timothy | |
| dc.contributor.committeemember | Shearer, Jane | |
| dc.date | 2022-06 | |
| dc.date.accessioned | 2022-04-19T16:21:27Z | |
| dc.date.available | 2022-04-19T16:21:27Z | |
| dc.date.issued | 2022-04 | |
| dc.description.abstract | Mitochondrial dysfunction can lead to disruption of cellular homeostasis. This can occur because of an existing disease or condition like inflammation and DNA mutations; however, despite not being the main factor initiating the disease (e.g., inflammatory bowel diseases (IBDs)), the mitochondria play an important role in promoting or dampening its severity. Therefore, mitochondrial dysfunction is often not considered diagnostic for a specific condition but reflects the general wellbeing of the cell. This makes analysis of mitochondrial function/dysfunction critical in understanding normal homeostasis and disease, prompting the idea that controlling mitochondrial function is a promising therapeutic target in diseases. In a healthy gut, resident commensal bacteria affect cellular functions, with bacterial fermentation products such as short chain fatty acids (SCFAs) having a wide range of benefits including enhancing mitochondrial biogenesis. However, dysbiosis in the gut of IBD patients decrease the abundance of SCFAs-producing bacterial species, especially butyrate producing bacteria like clostridia. Adherent invasive E. coli (AIEC) is a pathobiont strain of E. coli associated with Crohn’s disease (CD) and was implicated in the pathogenesis of CD through inducing proinflammatory responses. Research from the McKay laboratory demonstrated that in gut epithelial cells (i.e., the T84 human cell line) E. coli LF82 infection caused severe mitochondrial dysfunction. We hypothesized that sodium butyrate (NaB) might protect against E. coli LF82-induced mitochondrial dysfunction. To investigate this, parameters of mitochondrial functions like mitochondrial morphology and membrane potential were measured. E. coli LF82 infection in colonic epithelium induced dramatic mitochondrial fragmentation, loss in mitochondrial membrane potential and reduced mRNA expression of mitochondrial biogenesis regulator, however, NaB treatment protected against E. coli LF82-induced mitochondrial dysfunction. Attempting to identify the mechanism by which NaB protected mitochondrial functions against E. coli LF82 infection, we found that NaB protective effect was blocked when cells were pretreated with Gi subunit inhibitor pertussis toxin (PTX), emphasizing the role of NaB as a ligand for G protein-coupled receptors (GPCRs) GPR41 and GPR109A in this mechanism. The data in this thesis represent a novel perspective on the interaction between a commensal bacteria-derived metabolite and a CD-pathobiont through mitochondrial functions laying the foundation for future studies. | en_US |
| dc.identifier.citation | Hamed, S. (2022). Butyrate Alleviates Crohn's Diseases' adherent invasive E coli-induced mitochondrial dysfunction in intestinal epithelium (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/39686 | |
| dc.identifier.uri | http://hdl.handle.net/1880/114557 | |
| dc.language.iso | eng | en_US |
| dc.publisher.faculty | Cumming School of Medicine | en_US |
| dc.publisher.institution | University of 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. | en_US |
| dc.subject | Mitochondria | en_US |
| dc.subject | Mitochondrial Dysfunction | en_US |
| dc.subject | E. coli LF82 | en_US |
| dc.subject | Adherent invasive E. coli | en_US |
| dc.subject | Crohn's Disease | en_US |
| dc.subject.classification | Education--Health | en_US |
| dc.subject.classification | Education--Sciences | en_US |
| dc.title | Butyrate Alleviates Crohn's Diseases' Adherent Invasive E coli-Induced Mitochondrial Dysfunction in Intestinal Epithelium | en_US |
| dc.type | master thesis | en_US |
| thesis.degree.discipline | Medicine – Gastrointestinal Sciences | en_US |
| thesis.degree.grantor | University of Calgary | en_US |
| thesis.degree.name | Master of Science (MSc) | en_US |
| ucalgary.item.requestcopy | true | en_US |