Abstract
Inflammatory bowel disease (IBD) is an incurable gastrointestinal illness. The pervasive impacts of IBD can lead to significant abdominal symptoms, disability, impaired quality of life and psychological distress. Most IBD treatments aim to dampen gut inflammation and thus gold standard methods of IBD assessment focus on evaluating the presence and extent of inflammation within the gastrointestinal tract. Objective measures of IBD activity rely on endoscopic investigations that are invasive and expensive. Non-invasive biomarkers of gut inflammation are becoming increasingly accepted as surrogate treatment targets and this is a field of growing interest.
The associations between objectively measured gut inflammation and the total burden of IBD remains unclear. Holistic IBD assessment should ideally measure disease activity and the impacts of this illness on an individual’s life. Disease indices reflecting these factors would thus be able to measure overall severity of IBD and may help prognosticate the longitudinal course of illness. There are no existing, validated tools that accurately encapsulate IBD severity. This thesis investigated a novel biomarker of IBD activity, explored the relationship of the inflammatory and non-inflammatory burden of IBD, and assessed an index aiming to define the severity of IBD.
Chapter 1 explored mechanisms of gut inflammation in IBD, currently available methods of disease assessment, and important predictors of IBD prognosis. Chapter 2 provided an overview of recruitment procedures and study related investigations for the cohorts presented in this thesis.
The pathophysiology of IBD is mediated, in part, by the innate immune system and the actions of the neutrophil enzyme myeloperoxidase. Thus, the role of faecal myeloperoxidase as a non-invasive biomarker of IBD activity was investigated in Chapter 3. The utility of faecal biomarkers in predicting the longitudinal course of illness was explored in Chapter 4.
Chapter 5 evaluated the associations between objective IBD activity and symptoms of psychological stress, depression, and anxiety. Chapter 6 investigated the associations between objective IBD activity and sexual dysfunction, an often under-reported consequence of living with this disease.
Chapters 7 to 9 aimed to validate the Disease Severity Index (DSI) for IBD and explored its utility in reflecting gut inflammation, the impact of disease on the patient, and ability to prognosticate the disease course. Chapter 10 provided a summary of the pertinent findings of this thesis and future directions for this research.
The key results of this thesis were that:
1. Faecal myeloperoxidase was an accurate biomarker of gut inflammation in IBD.
2. Faecal biomarkers more accurately predicted longitudinal IBD complications compared to clinical disease activity alone.
3. The non-inflammatory burden of IBD (inclusive of psychological distress and sexual dysfunction) was not associated with the level of gut inflammation.
4. The DSI was a valid and reliable instrument that reflected objective gut inflammation, IBD and psychological symptoms, patient reported outcome measures, and predicted a more complicated disease course.
The novel findings of this thesis will make important contributions to the current understanding of IBD and provides insight into how non-invasive disease assessment can help to deliver holistic care for patients with IBD.