Effect of Bacterial Species Associated with Major Depressive Disorder on Emotionality Behaviors, Microbiome Structure, and Metabolism in Gnotobiotic Mouse Models

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dc.contributor.advisorMcCoy, Kathy D
dc.contributor.advisorTaylor, Valerie H
dc.contributor.authorCooke, Noah C.A.
dc.contributor.committeememberHirota, Simon
dc.contributor.committeememberMcGirr, Alexander
dc.contributor.committeememberSharkey, Keith A
dc.contributor.committeememberSavchenko, Alexei
dc.dateFall Convocation
dc.date.accessioned2023-05-11T05:30:30Z
dc.date.embargolift2023-08-17
dc.date.issued2021-08-17
dc.description.abstractMajor depressive disorder (MDD) is a prevalent disease, and antidepressants lack efficacy in many patients, motivating investigation for new therapeutic modalities. Altered microbiome composition and metabolism have been implicated in MDD, but the specific species and metabolites involved, and their mechanisms of effect, remain elusive. We set out to test whether two bacterial species correlated with MDD alter emotionality-related behaviors in stress-naïve and chronic stress-exposed mice, when added to the stable defined moderately diverse mouse microbiome 2 (sDMDMm2) consortium. We hypothesized that Lachnospiraceae bacterium would increase, and Faecalibacterium prausnitzii would decrease, these behaviors in both conditions. Further, we hypothesized that these behavioural effects would coincide with effects on microbiome composition and metabolism. To assess emotionality-like behavior, we established a gnotobiotic behavioral system comprised of five tests and the chronic variable stress (CVS) model for studying depression. L. bacterium did not alter depressive and anxiety-like behaviors in the stress-naïve condition. In the CVS condition, an increase in anxiety-like behavior was seen in one assay, the elevated plus maze test, in one preliminary experimental replicate. Illumina 16S V4 amplicon sequencing revealed that L. bacterium significantly altered microbiome composition. Hydrophilic interaction liquid chromatography with mass spectrometry (HILIC-MS/MS) also revealed a significant effect of L. bacterium on microbiome and serum metabolism. This thesis offers a novel methodological approach to investigate causal relationships between bacterial species and emotionality-related behaviors, and to identify microbial candidates for microbiome-targeted therapies for MDD.Keywords: microbiome, Lachnospiriceae bacterium, Major Depressive Disorder, Metabolism.
dc.identifier.citationCooke, N. C. A. (2021). Effect of Bacterial Species Associated with Major Depressive Disorder on Emotionality Behaviors, Microbiome Structure, and Metabolism in Gnotobiotic Mouse Models (Master thesis). University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca .
dc.identifier.urihttp://hdl.handle.net/1880/116420
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/dspace/41264
dc.language.isoEnglish
dc.publisher.facultyCumming School of Medicine
dc.subjectMicrobiome
dc.subjectMajor Depressive Disorder
dc.subjectDepression
dc.subjectBehavioral Neuroscience
dc.subjectBacteria
dc.subject.classificationHealth Sciences--Mental Health
dc.subject.classificationBiology--Physiology
dc.subject.classificationBiology--Neuroscience
dc.titleEffect of Bacterial Species Associated with Major Depressive Disorder on Emotionality Behaviors, Microbiome Structure, and Metabolism in Gnotobiotic Mouse Models
dc.typemaster thesis
thesis.degree.disciplineMedicine – Gastrointestinal Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
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