Pathophysiology of Diverticular Disease

The Role of Intestinal Microbiota Composition and Intestinal Permeability in the Development of (Complicated) Diverticular Disease.

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.

Study Overview

• Status: Unknown
• Conditions: Diverticulitis; Colonic Diverticula

• Study Type: Observational
• Enrollment (Anticipated): 210

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202 AZ
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients referred to the hospital by their general practitioner

Description

Inclusion Criteria:

• Age ≥ 50 years and ≤ 75 years
• Scheduled for colonoscopy
• Written informed consent
• Patient group: The presence of diverticulosis, diagnosed during the scheduled colonoscopy
• Control group: During the scheduled colonoscopy, diverticulosis or other
• gastrointestinal and liver diseases are absent. In other words, the
• colonoscopy is qualified as a 'normal' colonoscopy.

Exclusion Criteria:

• Age < 18 years
• Presence of gastrointestinal and liver diseases, such as inflammatory bowel disease.
• Use of NSAID's and proton pump inhibitors, during the 5-day time period prior to endoscopy.
• Alcohol intake above 14 consumptions per week for males and 7 consumption per week for females
• (Sub)total colectomy or hemicolectomy.
• Refusal to participate in this study

Study Plan

How is the study designed?

Design Details

• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Controls; No diverticular disease or other gastrointestinal and liver diseases
Uncomplicated diverticular disease
History of complicated diverticular disease
Current complicated diverticular disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
intestinal (luminal and mucosal) microbiota composition	up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Expression of tight junction proteins	up to 2 years
Intestinal permeability	up to 2 years

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: A. M. Masclee, MD, PhD, Maastricht University Medical Center; Study Chair: D. Jonkers, PhD, Maastricht University Medical Center; Study Chair: R. C. Deutz, MD, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Anticipated): October 1, 2013
• Study Completion (Anticipated): October 1, 2014

Study Registration Dates

• First Submitted: December 14, 2011
• First Submitted That Met QC Criteria: December 14, 2011
• First Posted (Estimate): December 16, 2011

Study Record Updates

• Last Update Posted (Estimate): January 5, 2012
• Last Update Submitted That Met QC Criteria: January 4, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Diverticulitis; Colonic diverticula
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Diverticulitis; Diverticulum; Diverticular Diseases; Diverticulosis, Colonic; Diverticulum, Colon
• Other Study ID Numbers: 11-2-058