Microbial dysbiosis alters serotonin signalling in a post-inflammatory murine model of visceral pain

Roth, Timothy Douglas

Microbial dysbiosis alters serotonin signalling in a post-inflammatory murine model of visceral pain

dc.contributor.advisor	Sharkey, Keith
dc.contributor.author	Roth, Timothy Douglas
dc.contributor.committeemember	Nasser, Yasmin
dc.contributor.committeemember	Altier, Christophe
dc.date	2024-11
dc.date.accessioned	2024-07-11T17:33:01Z
dc.date.available	2024-07-11T17:33:01Z
dc.date.issued	2024-07-10
dc.description.abstract	Inflammatory bowel disease (IBD) is a chronic disorder characterized by inflammation of the gastrointestinal tract, affecting a growing number of individuals worldwide. Despite achieving endoscopic remission, many IBD patients continue to experience visceral pain, suggesting underlying mechanisms beyond inflammation. One hypothesis implicates alterations in gut microbiota post-inflammation, leading to dysregulated serotonin (5-HT) signalling within the gut and heightened pain sensitivity. This thesis investigated this hypothesis using a mouse model of IBD in remission associated with visceral pain to explore changes in enterochromaffin cell populations, gene expression related to 5-HT synthesis, transport, and degradation, as well as 5-HT concentration and its metabolites. Additionally, fecal microbiota transplant (FMT) experiments were performed using stool from DSS-treated mice, alongside comparative analyses with germ-free (GF) mice, to delineate the impact of the microbiota on post-inflammatory pain in IBD and establish a baseline for gut microbiota effects on 5-HT signalling. High-performance liquid chromatography (HPLC) was utilized to assess 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) tissue concentrations, and enzyme-linked immunosorbent assay (ELISA) was employed to determine 5-HT release dynamics in the gut. Our findings revealed region-specific differences in 5-HT release in the terminal ileum, proximal colon, and distal colon, suggesting localized alterations in 5-HT signalling post-inflammation. Additionally, GF mice displayed distinct patterns of altered gene expression and 5-HT/5-HIAA concentration compared to conventionally colonized counterparts, underscoring the pivotal role of gut microbiota in modulating 5-HT metabolism and signalling. FMT experiments allowed us to assess the impact of dysbiotic microbiota on post-inflammatory pain. Surprisingly, we found no significant differences in gene expression between control and DSS-treated FMT groups, suggesting resilience of the host to changes in microbiota composition. However, we observed differences in 5-HT release dynamics between FMT groups, indicating potential microbiota-driven alterations in neuronal signalling pathways. Overall, we found alterations in 5-HT signalling in the recovery model of DSS-induced colitis. These findings enhance our understanding of the pathophysiology of IBD-related pain, highlighting the complex interplay between gut microbiota and 5-HT signalling after a period of intestinal inflammation.
dc.identifier.citation	Roth, T. D. (2024). Microbial dysbiosis alters serotonin signalling in a post-inflammatory murine model of visceral pain (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/119171
dc.identifier.uri	https://doi.org/10.11575/PRISM/46767
dc.language.iso	en
dc.publisher.faculty	Cumming School of Medicine
dc.publisher.institution	University of Calgary
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	5-ht
dc.subject	serotonin
dc.subject	dysbiosis
dc.subject	IBD
dc.subject	enterochromaffin
dc.subject	murine
dc.subject	visceral pain
dc.subject	microbiota
dc.subject.classification	Education--Health
dc.subject.classification	Neuroscience
dc.subject.classification	Psychology--Physiological
dc.title	Microbial dysbiosis alters serotonin signalling in a post-inflammatory murine model of visceral pain
dc.type	master thesis
thesis.degree.discipline	Medicine – Neuroscience
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.