- Title
- Investigating colonic spirochaetosis in association with irritable bowel syndrome
- Creator
- Fan, Kening
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2023
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) disorders that significantly impacts 9% of the general population worldwide. While its pathophysiology remains largely unclear, an association between IBS and colonic spirochaetosis (CS) has been reported. CS is a colonic bacterial infection whose pathogenesis in human is still debated and limited studies are available regarding the clinical impact and pathology of this infection. Hypothesis and aims: We hypothesised that CS is a cause of GI symptoms in a subset of IBS patients. Therefore, we aimed to perform a systematic review of CS to investigate the association between CS and GI symptoms. We also aimed to characterise the mucosal immune response and clinical symptom profiles in a cohort of patients with CS compared to CS-free controls. In addition, we aimed to identify specific spirochaetes species in CS patients and differentiate the species regarding their association with certain immune responses and clinical impacts. Methods: Systematic review was performed following the PRISMA guidelines, meta-analysis of case-control studies were conducted where possible. Formalin fixed, paraffin-embedded (FFPE) colonic biopsies from 20 CS patients, 20 matched CS-free controls and 11 normal controls were stained for eosinophils, mast cells and intra-epithelial lymphocytes. Peak cell numbers and degranulation scores of these immune cells were quantified in the intra-epithelial, intra-crypt and lamina propria areas. Eotaxin-1, mast cell tryptase and eosinophil cationic protein (ECP) expressions were semi-quantified by Halo Area Quantification algorithm. DNA was recovered from the FFPE colonic biopsies from CS patients and species-specific PCR was performed to identify spirochaete species. Results: Systematic review and meta-analysis found that CS is associated with higher risks of diarrhoea, abdominal pain and diagnosis of IBS. Histology analysis showed that CS patients had increased eosinophils, mast cells and intra-epithelial lymphocytes compared to CS-free controls. Spirochaete colonisation co-localised with higher epithelial cell-expressed eotaxin-1, sub-epithelial ECP and eosinophil major basic protein (EMBP) accumulation. Correlation analysis found that levels of eosinophils and mast cells were negatively correlated. CS infection was independently associated with blood in stool and diverticulosis in studied patient cohorts. B. aalborgi was identified as the main species of spirochaete in our cohort of CS patients. B. pilosicoli and B. aalborgi infections showed differences in their mucosal immune responses as well as clinical impacts in infected patients. Conclusion: CS is likely to play a role in the development of IBS-like symptoms in infected patients and understanding the pathophysiology of CS infections revealed novel disease mechanisms of IBS that may lead to better management of disease in these patients.
- Subject
- Irritable bowel syndrome; colonic spirochetosis; gastrointestinal (GI) disorders; pathophysiology
- Identifier
- http://hdl.handle.net/1959.13/1488643
- Identifier
- uon:52496
- Rights
- Copyright 2023 Kening Fan
- Language
- eng
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 22 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 311 KB | Adobe Acrobat PDF | View Details Download |