Colonic Diverticula Are Not Associated With Mucosal Inflammation or Chronic Gastrointestinal Symptoms

Anne F. Peery; Temitope O. Keku; Cassandra Addamo; Amber N. McCoy; Christopher F. Martin; Joseph A. Galanko; Robert S. Sandler

Disclosures

Clin Gastroenterol Hepatol. 2018;16(6):884-891. 

In This Article

Abstract and Introduction

Abstract

Background & Aims: Colonic diverticulosis has been reported to be associated with low-grade mucosal inflammation, possibly leading to chronic gastrointestinal symptoms. However, there is poor evidence for this association. We aimed to determine mucosal inflammation and whether diverticula are associated with chronic gastrointestinal symptoms. We explored whether inflammation was present among symptomatic participants with and without diverticula.

Methods: We analyzed data from a prospective study of 619 patients undergoing a screening colonoscopy from 2013 through 2015 at the University of North Carolina Hospital in Chapel Hill, North Carolina. Among our participants, 255 (41%) had colonic diverticula. Colonic mucosal biopsy specimens were analyzed for levels of interleukin 6 (IL6), IL10, and tumor necrosis factor messenger RNAs by quantitative reverse-transcriptase polymerase chain reaction, and numbers of immune cells (CD4+, CD8+, CD57+, and mast cell tryptase) by immunohistochemistry. Gastrointestinal symptoms were assessed using Rome III criteria. Proportional odds models were used to estimate odds ratios (ORs) and 95% confidence interval (CIs).

Results: After adjustment for potential confounders, there was no association between diverticulosis and tumor necrosis factor (OR, 0.85; 95% CI, 0.63–1.16), and no association with CD4+ cells (OR, 1.18; 95% CI, 0.87–1.60), CD8+ cells (OR, 0.97; 95% CI, 0.71–1.32), or CD57+ cells (OR, 0.80; 95% CI, 0.59–1.09). Compared with controls without diverticulosis, biopsy specimens from individuals with diverticulosis were less likely to express the inflammatory cytokine IL6 (OR, 0.59; 95% CI, 0.36–0.96). There was no association between diverticulosis and irritable bowel syndrome (OR, 0.53; 95% CI, 0.26–1.05) or chronic abdominal pain (OR, 0.68; 95% CI, 0.38–1.23). There was no evidence for inflammation in patients with symptoms when patients with vs without diverticulosis were compared.

Conclusions: We found no evidence that colonic diverticulosis is associated with mucosal inflammation or gastrointestinal symptoms. Among patients with symptoms and diverticula, we found no mucosal inflammation.

Introduction

Colonic diverticula are common in the United States. After the age of 60, more than 50% of individuals in the Unites States have colonic diverticulosis.[1,2] Although colonic diverticulosis can be complicated by the overt inflammation of acute diverticulitis, there is some thought that colonic diverticulosis is associated with low-grade mucosal inflammation.[3] Moreover, this low-grade diverticular inflammation is believed to contribute to chronic gastrointestinal symptoms.[3] The term symptomatic uncomplicated diverticular disease (SUDD) has been applied to chronic gastrointestinal symptoms attributed to colonic diverticulosis in the absence of overt inflammation.[3]

Despite the growing amount of literature associating colonic diverticulosis with low-grade mucosal inflammation and SUDD, the evidence for these associations is poor. A single pilot study found that colonic diverticulosis was associated with an increase in colonic macrophages compared with controls.[4] This study was limited to bivariate comparisons that did not control for confounding variables. The evidence for chronic gastrointestinal symptoms attributed to colonic diverticulosis in Western populations is limited. A population-based study found an association between diverticulosis and diarrhea-predominant irritable bowel syndrome, but only in patients older than age 60.[5] Another study found an association, however, diverticulosis status was abstracted from charts.[6] The evidence that low-grade diverticular inflammation is associated with chronic gastrointestinal symptoms is very low quality and includes a case series[7] and case–control studies with inappropriate controls.[4,8] Determining whether colonic diverticulosis is associated with chronic mucosal inflammation and chronic gastrointestinal symptoms has clinical implications. The chronic inflammation argument is used as a rationale for treating patients with SUDD with mesalamine.[9]

To assess whether colonic diverticula are associated with markers of colonic mucosal inflammation, we conducted a prospective study of patients undergoing a complete screening colonoscopy that included mucosal biopsies. We also examined whether colonic diverticula are associated with chronic gastrointestinal symptoms and explored whether markers of mucosal inflammation were increased among participants with chronic gastrointestinal symptoms. To focus on colonic diverticulosis, we excluded any individual with a history of diverticulitis or with overt diverticular inflammation.

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