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dc.contributor.authorAlizadeh, Madeline
dc.date.accessioned2024-07-10T12:35:32Z
dc.date.available2024-07-10T12:35:32Z
dc.date.issued2024
dc.identifier.urihttp://hdl.handle.net/10713/22583
dc.descriptionUniversity of Maryland, Baltimore, School of Medicine, Ph.D. 2024.en_US
dc.description.abstractInflammatory Bowel Diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are increasingly common and characterized by inflammation of the gastrointestinal (GI) tract. A subset of patients with IBD also develop non-intestinal symptoms, known as extra intestinal manifestations (EIMs). The most common EIM, IBD-associated spondyloarthritis (IAA), occurs in up to 40-50% of patients within 30 years of diagnosis, and can be incredibly debilitating. However, it is poorly understood why some patients develop EIMs, but others do not. GI mucosal and stool microbial richness are decreased in IBD and non-IBD spondyloarthritis, and some overlapping changes indicate key microbial factors may drive both conditions. IBD disease location can be predicted by microbial profiles, and IAA tends to be associated with location of disease involvement, suggesting the region-specific intestinal microbiome plays a role in IAA. However, the relationship between the microbiome and IAA remains unexplored. I hypothesized that within the colon, the regional microbiome promotes IAA. To test this hypothesis, I first assessed clinical characteristics of participants in the SPARC-IBD cohort, and found EIMs were associated with increased biologic cycling, and that IAA was associated with a number of clinical factors, including right-sided disease involvement. I then enrolled 182 patients with IBD (53 with IAA) scheduled for clinical colonoscopy and obtained tissue biopsies from across the intestinal tract. 16S V3V4 rRNA gene amplicon sequencing was generated from tissue samples, and a variety of statistical tools were used to assess differences between those with and without IAA. Sample clustering was predominantly participant driven, with similar taxa present across the colon. Alpha-diversity significantly differed based on IBD type (CD & IBD-type undetermined (IC) < UC). Models assessing taxa associated with IAA, accounting for IBD type, sex, and the interaction between these factors and taxa, further revealed sex- specific interactions, where females and males with IAA displayed decreased Roseburia intestinalis and enrichment of Corynebacterium, respectively. This is the first study to compare the intestinal mucosal microbiome in subjects with and without IAA, offering an increased understanding of the potential role of the microbiome in IAA, and is a pivotal first step in driving biomarker identification necessary for new precision treatment for IBD.en_US
dc.language.isoen_USen_US
dc.subject.meshInflammatory Bowel Diseasesen_US
dc.subject.meshUlcerative Colitisen_US
dc.subject.meshCrohn Diseaseen_US
dc.subject.meshMicrobiotaen_US
dc.subject.meshSpondylarthropathiesen_US
dc.titleExploring the Role of the Intestinal Microbiome in IBD-Associated Arthritisen_US
dc.typedissertationen_US
dc.date.updated2024-06-27T22:12:39Z
dc.language.rfc3066en
dc.contributor.advisorvon Rosenvinge, Erik C.
dc.contributor.advisorRavel, Jacques, Ph.D.
refterms.dateFOA2024-07-10T12:35:33Z


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