Developing a Novel Approach to Subgrouping People with Irritable Bowel Syndrome: Moving Beyond Stool Pattern Alone

Introduction: Conventionally, irritable bowel syndrome (IBS) is subgrouped using predominant stool pattern, yet it is a complex disorder, with multiple biopsychosocial contributors. This thesis aimed to explore an alternative approach to subgrouping by incorporating factors beyond stool pattern alone. Methods: Two network meta-analyses, examining the relative efficacy of secretagogues for IBS-C, and of pharmacological therapies for IBS-D or IBS-M, respectively, were conducted to evaluate the merits of subgrouping people with IBS using stool pattern alone. A large cohort of people who self-identified as having IBS was recruited, and the clinical and psychological differences between individuals based on the Rome IV versus Rome III criteria were examined. In the same cohort, latent class analysis was used to derive new IBS subgroups by combining data on gastrointestinal symptoms and psychological health. Longitudinal follow-up was undertaken to assess the natural history and prognostic value of these new subgroups. Results: The efficacy of treatments for both IBS-C and IBS-D or IBS-M was modest overall, with little difference between individual drugs. In total, 1375 individuals who self-identified as having IBS were recruited. Individuals with Rome IV-defined IBS had significantly more severe symptoms and poorer psychological health, compared with those who only met the Rome III criteria for IBS. In both Rome IV and Rome III-defined IBS, people could be divided into seven distinct subgroups defined by a pattern of gastrointestinal symptoms (diarrhoea-related, constipation-related, or mixed) and further differentiated by the presence of abdominal pain not relieved by defaecation, and by the extent of psychological comorbidity. Follow-up showed that people in clusters with high psychological burden at baseline had significantly more severe symptoms at follow-up, which had a greater impact on daily activities, received a significantly higher mean number of subsequent treatments, and were significantly more likely to consult a doctor than people in clusters with low psychological burden. Conclusions: Directing treatment according to predominant stool pattern alone results in modest outcomes at best. Additional factors, such as psychological health, may influence treatment response, and people with IBS can be divided into unique subgroups characterised by differences in gastrointestinal symptoms, extra-intestinal symptoms, and mood. Subgroups with higher psychological burden were predictive of a more severe disease course. Personalising treatment according to these novel subgroups, including earlier use of psychological therapies, may improve outcomes in IBS.