Antibiotic Reduction of Bacterial β-Glucuronidase Activity in the Murine Gut Prevents and Reverses Mycophenolate Mofetil-Induced Gastrointestinal Toxicity

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dc.contributor.advisorGreenway, Steven C.
dc.contributor.authorTaylor, Michael Robert
dc.contributor.committeememberLewis, Ian A.
dc.contributor.committeememberHirota, Simon Andrew
dc.date2018-11
dc.date.accessioned2018-09-06T14:10:28Z
dc.date.available2018-09-06T14:10:28Z
dc.date.issued2018-08-27
dc.description.abstractMycophenolate mofetil (MMF) is an important immunosuppressive drug widely used post- transplantation, but whose use is often limited by gastrointestinal (GI) side effects including diarrhea, weight loss and colitis. The etiology of this GI toxicity has not been fully explained although we have shown in the mouse that an intact microbiome is required. This thesis developed and tested a potential mechanism, hypothesizing that bacterial conversion of the MMF metabolite mycophenolic acid glucuronide (MPAG) to mycophenolic acid (MPA) in the colon is responsible for the GI toxicity caused by MMF. Vancomycin both prevented and reversed MMF- induced GI toxicity and we characterized its effect on the intestinal microbiota in MMF-treated mice. Vancomycin eliminated many β-glucuronidase-producing bacteria, resulting in decreased hydrolysis of MPAG to MPA that was also associated with decreased weight loss and reduced colonic inflammation and injury. These findings outline a mechanism permitting interventions to improve MMF tolerance.en_US
dc.identifier.citationTaylor, M. R. (2018). Antibiotic Reduction of Bacterial β-Glucuronidase Activity in the Murine Gut Prevents and Reverses Mycophenolate Mofetil-Induced Gastrointestinal Toxicity (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32883en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/32883
dc.identifier.urihttp://hdl.handle.net/1880/107705
dc.language.isoeng
dc.publisher.facultyCumming School of Medicine
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity 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.subjectTransplantation
dc.subjectMycophenolate Mofetil (MMF)
dc.subjectGastrointestinal Toxicity
dc.subjectMicrobiome
dc.subjectBacterial β-Glucuronidase
dc.subject.classificationMicrobiologyen_US
dc.subject.classificationHealth Sciencesen_US
dc.titleAntibiotic Reduction of Bacterial β-Glucuronidase Activity in the Murine Gut Prevents and Reverses Mycophenolate Mofetil-Induced Gastrointestinal Toxicity
dc.typemaster thesis
thesis.degree.disciplineMedical Science
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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