Colonic Diverticular Disease and the Role of Inflammation

Despite colonic diverticula being the world's fifth most histologically observed gastrointestinal alteration, the aetiopathophysiology is still poorly understood. While complications of colonic diverticula only affect an estimated 4% of patients with colonic diverticulosis, colonic diverticulitis has a high burden on the health care system and afflicted individuals. It is, therefore, essential to understand the underlying causes of diverticular disease, including the contribution of diverticular inflammation. The primary aim of this thesis was to improve understanding of the current and potential role of inflammation in colonic diverticulosis and diverticular disease aetiopathogenesis and associated patient mortality. The first key finding of this thesis was an absence of definitive evidence of mucosal-associated microbiota associations with inflammatory cells in colonic diverticulae. The systematic review indicated that substantial methodological heterogeneity may have influenced findings, with consistent study design and exploration of microbial metabolites in microbiome-immune research in diverticular disease recommended. This thesis reported the presence of eosinophilia within the mucosal tissue at the base of colonic diverticulae, from patients with asymptomatic diverticulosis through to complicated disease. Increased eosinophil cell numbers in the submucosa were also found in samples from those with complicated diverticulitis. Utilising a nationwide cohort, this thesis demonstrated that patients with diagnostic colonic diverticula and inflammation at histology have an increased prevalence of mortality within the first twelve months post-diagnosis. However, when age, sex and comorbidities are adjusted for, and the cohort extended to include patients with colonic diverticulosis (asymptomatic incidental) and uncomplicated diverticulitis mortality risk was not significantly different to non-diverticular patients, except for patients with complicated disease who still had a two-times higher risk of mortality. In conclusion, this thesis synthesises new data that provides insight into the role of inflammation within colonic diverticular disease and the association of inflammation with the risk of mortality for patients with colonic diverticular disease. Proposed directions for future research include validation of studies from this thesis, followed up with longitudinal human studies to investigate whether tissue eosinophilia contributes to diverticular formation and whether eosinophilic inflammation contributes to colonic diverticular complications that increase patient mortality.