Rimmer, Peter 
ORCID: 0000-0002-0528-6154
(2025).
Appraising novel host and gut microbial interactions at Inflammatory Bowel Disease onset: Exploring the role of galectins and the microbiome.
University of Birmingham.
Ph.D.
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Abstract
Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of increasing prevalence. Its aetiological basis is multifactorial, with interactions between the host immune system and gut microbiota, alongside genetic and environmental factors of key importance. Despite our increasing understanding, the consistent delivery of early diagnosis and the development of biomarkers that can predict disease course to facilitate timely personalised treatment both remain elusive.
In this thesis, I explore what is known about the gastrointestinal microbiome at IBD onset, alongside our current understanding of the immune functions of a group of proteins, beta-galactoside binding lectins, and how they relate to IBD. This is achieved via systematic review and meta-analysis relating to the microbiome, and a literature review concerning galectins.
I describe the cross-site implementation of a novel rapid-access pathway for IBD diagnosis in one of the largest NHS trusts in the UK and explore how current clinical tools can be better utilised for referral triage, resource allocation and more detailed baseline assessment. I present a comprehensive prospective analysis of how best to utilise the clinical history and tools such as Faecal Calprotectin (FCP) to optimally triage referrals. Furthermore, I introduce the first validation of the IBD Disk as a means of screening for significant psychological disturbance, whilst also identifying those at risk of adverse treatment outcomes.
Patients recruited to research from this clinical pathway provided faecal samples to allow the detailed evaluation of the treatment-naïve gut microbiome using both 16S ribosomal RNA (rRNA) sequencing and shotgun metagenomics. I have integrated this dataset with published pre-treatment IBD microbiome data to present the largest analysis of the role of microbiome at IBD onset in the literature to date. The longitudinal follow up and outcome data from our own Birmingham cohort has allowed us to build up on the findings from the pooled dataset and demonstrate novel microbial associations with disease activity, disability, and treatment outcomes.
In this same patient cohort, I have undertaken the first study of serum galectin levels in IBD patients prior to the initiation of treatment. This study has elucidated the close association of baseline galectin-9 levels to disease severity and subsequent treatment response, outperforming established clinical indices in this regard. I have, for the first time, integrated serum galectin expression with the gut microbiome at IBD onset, both in terms of overall diversity and enrichment or depletion of specific bacterial taxa. For example, serum galectin-9 levels positively correlate with the abundance of established pathobionts including Ruminococcus gnavus. I have developed models of this integrated data able to accurately predict the subsequent failure of conventional therapies in patients presenting with IBD.
The studies performed in this thesis contribute to the ongoing efforts to deliver earlier and personalised care to patients presenting with IBD. I aim to build upon the data presented through my ongoing research objectives, such as with targeting microbiome intervention, as I embark upon my consultant career.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
| Supervisor(s): |
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| Licence: | All rights reserved | |||||||||
| College/Faculty: | Colleges > College of Medicine and Health | |||||||||
| School or Department: | Institute of Cardiovascular Sciences | |||||||||
| Funders: | Other | |||||||||
| Other Funders: | F. Hoffmann La Roche, National Institute for Health Research, Guts UK | |||||||||
| Subjects: | Q Science > QR Microbiology Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine |
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| URI: | http://etheses.bham.ac.uk/id/eprint/16382 |
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- Appraising novel host and gut microbial interactions at Inflammatory Bowel Disease onset: Exploring the role of galectins and the microbiome. (deposited 04 Mar 2026 10:54) [Currently Displayed]
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