Microbial Dynamics and Metabolism in Gnotobiotic Mouse Models of Autism Spectrum Disorder

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dc.contributor.advisorMcCoy, Kathleen D.
dc.contributor.authorYee, Jenine R.
dc.contributor.committeememberReimer, Raylene A.
dc.contributor.committeememberSharkey, Keith A.
dc.dateFall Convocation
dc.date.accessioned2023-05-11T04:01:59Z
dc.date.embargolift2023-09-17
dc.date.issued2021-09-17
dc.description.abstractAutism Spectrum Disorder (ASD) is a highly heterogeneous disorder with diagnoses based on core behaviours centering on limited social interest, anxiety, and obsessive and repetitive movements. Recent studies have revealed a potential link between composition of the gut microbiota and ASD. The bacterial species Clostridium innocuum was found to be highly abundant in children with ASD and significantly reduced following fecal microbiota transplantation. The maternal immune activation (MIA) model was chosen as an experimental model to investigate whether C. innocuum would alter susceptibility to ASD. As the MIA model has been shown to require segmented filamentous bacterium (SFB) induction of Interleukin 17 (IL-17) during pregnancy, a co-colonization system was required. In this thesis, we investigated the dynamics between SFB and two different strains of C. innocuum, one isolated from an ASD participant and the other isolated from a healthy donor. In this mouse model, SFB co-colonized similarly with either strain of C. innocuum. To further investigate the effect presence of the two C. innocuum strains, serum metabolite profiles were analyzed using liquid chromatography-mass spectrometry for semi-untargeted metabolomics. Although serum samples from mice co-colonized with SFB and either of the two C. innocuum strains had similar metabolite profiles, significantly different metabolomic profiles were found following induction of maternal immune activation. Aspartate, hippurate and glycerol-3-phosphate were found to be significantly upregulated in the mice co-colonized with the C. innocuum isolated from an ASD participant when MIA was induced. These metabolites have been found in altered levels in children with ASD and ASD mouse models. Finally, in vitro cultures of other bacterial species found post-FMT produced metabolites involved with cellular repair, energy production and antioxidant activity such as N-acetyl-L-cysteine, glutathione, inosine and glutamine compared to media controls. Metabolites produced by the C. innocuum from the ASD participant may potentiate ASD behaviours and unravel targets for future research.
dc.identifier.citationYee, J. R. (2021). Microbial Dynamics and Metabolism in Gnotobiotic Mouse Models of Autism Spectrum Disorder (Master thesis). University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca .
dc.identifier.urihttp://hdl.handle.net/1880/116277
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/dspace/41121
dc.language.isoEnglish
dc.publisher.facultyCumming School of Medicine
dc.subjectAutism Spectrum Disorder
dc.subjectMaternal Immune Activation
dc.subjectMetabolomics
dc.subjectGut microbiome
dc.subjectClostridium innocuum
dc.subject.classificationHealth Sciences--Human Development
dc.subject.classificationHealth Sciences--General
dc.subject.classificationHealth Sciences--Immunology
dc.subject.classificationDevelopmental
dc.titleMicrobial Dynamics and Metabolism in Gnotobiotic Mouse Models of Autism Spectrum Disorder
dc.typemaster thesis
thesis.degree.disciplineMedicine – Gastrointestinal Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
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