Pathophysiology of Diverticular Disease

Overview

Colonic diverticular disease is a highly prevalent condition in Western populations. The prevalence increases age-dependently from 5% at 40 years to 65% by the age of 85 years (1-3). The majority remain asymptomatic. However, a significant proportion of the patient population develops complications, such as diverticulitis with or without symptoms (10-20%) (1, 4-10). Perforated diverticulitis is rare with an estimated incidence of 4 per 100.000 per year, but the associated mortality rate is 22% to 39% (9, 11, 12). In the United States, the complications related to diverticular disease account for 130.000 hospitalizations each year, resulting in substantial health care costs (13). In Europe, it is estimated that approximately 23.600 deaths per year can be attributed to complicated diverticular disease, and the mortality will probably increase in the future due to the aging population (15-17). Several case studies report an overall increase in the incidence of diverticulitis, based on the increase in hospitalizations (18). Kang et al, reported a 16% increased male admission rate and 12% female admission rate for diverticulitis, between 1989/1990 and 1999/2000 (19). Aging and the Western diet, low in fiber and high in fat, in combination with increased intraluminal pressure and alterations in colonic motility are considered important etiological factors. A disturbance in large bowel motility is suggested to be a common pathophysiological feature in IBS and diverticular disease (20, 21). Based on observations that IBD, subgroups of IBS and (symptomatic) diverticular disease share clinical symptoms, the hypothesis is derived that they might also share pathophysiological factors like low grade inflammation, changed microbiota composition and activity, and increased intestinal permeability. The identification of clinical and pathophysiological factors associated with an increased risk for complicated diverticular disease may help to identify patients with diverticular disease, prevent complications, develop strategies to improve quality of life and reduce the related health care costs. Therefore we aim to investigate the composition of luminal and mucosal intestinal microbiota and the intestinal permeability in the development of diverticular disease and complicated diverticular disease. We hypothesize that both the intestinal microbiota and intestinal permeability are altered in patients with (current- or previous history of complicated) diverticular disease.