Abstract
The awareness of irritable bowel syndrome (IBS) has increased exponentially online over the last decade, generating discussion surrounding disorders of gut-brain interaction (DGBI). IBS is a chronic disorder part of DGBI that affects between 3 and 11% of the world’s population and is characterised by altered bowel movements with abdominal pain. The lack of significant morphological changes in the gastrointestinal tissues, inconsistent symptom presentation and different subtypes which contribute to the range of symptoms seen in individuals makes diagnosis difficult. Additionally, IBS pathophysiology has genetic, environmental, dietary, psychological, and host and microbial contributors, resulting in a complex and multifaceted condition which requires high-level investigation. This research project aimed to investigate IBS using a genetic method as part of a larger body of research that uses the Christchurch IBS cOhort to investigate Mechanisms FOr gut Relief and improved Transit (Comfort) to analyse DGBI from multiple angles using a systems biology approach. The hypotheses were that the IBS-D (IBS-diarrhoea) and IBS-C (IBS-constipation) subtypes would have distinguishable gene expression profiles compared to healthy controls.
A gene panel consisting of 77 genes was constructed to assess for differential gene expression between individuals. Using colonic mucosal biopsies from the Comfort participants, gene counts were analysed for significant differences in gene expression. Following comprehensive statistical tests, a small set of genes, CLDN-3, FAAH and ZC3H12A, were differentially expressed between the controls and IBS subtypes. These 3 genes significantly differed between one or more of the subject groups. These genes regulate the intestinal barrier permeability and activation of the immune system cascade, supporting current knowledge of underlying pathophysiology and identifying new potential biomarker candidates for IBS diagnosis. This thesis’s findings can help design further studies focusing on a clinical genetic diagnostic test and gene targets for therapies to improve the health and well-being of these individuals.