Does Mucosal Inflammation Cause Diverticulosis?
Little is known about the pathogenesis of diverticulosis, and whether subacute colonic inflammation is involved.
Peery et al performed an observational study of 619 outpatients undergoing a first-time screening colonoscopy. Patients reported by an endoscopist to have diverticulosis (cases, 41%) were compared to patients without diverticulosis (controls).
Biopsy specimens were taken from normal-appearing mucosa in the sigmoid colon for assessment of immune markers and levels of mRNAs encoding cytokines. Gastrointestinal symptoms were assessed using Rome III diagnostic criteria for irritable bowel syndrome (IBS).
Peery et al found no association between diverticulosis and markers of subclinical colonic inflammation, including mRNA levels of tumor necrosis factor, CD4+ T cells, CD8+ T cells, or CD57+ cells. However, colonic mucosa from cases had a 42% reduced likelihood of expression of interleukin 6 (IL6) and a 33% reduced likelihood of expression of IL10.
There was no association between diverticulosis and IBS or chronic abdominal pain. Furthermore, no mucosal inflammation was found among patients with symptoms and diverticulosis compared with those having IBS or abdominal pain without diverticulosis.
In an analysis stratified by the location of colonic diverticula, biopsy specimens from individuals with only distal diverticula, compared with no colonic diverticula, had a 47% reduced likelihood of IL6 expression. Biospies from individuals with only proximal diverticula had a 64% reduced likelihood of CD8+ T-cell density and an increased ratio of CD4+ T cells to CD8+ T cells.
Of 42 participants who met the criteria for IBS, 11 had colonic diverticulosis and 31 did not. Of 63 participants with chronic abdominal pain, 22 had colonic diverticulosis and 41 did not have diverticulosis.
In an editorial that accompanies the article, Wenjie Ma and Andrew T. Chan write that the study provides convincing evidence for the lack of a relationship between subclinical mucosal inflammation and colonic diverticulosis among individuals without a history of diverticulitis and overt diverticular inflammation.
However, it is important to remember that this was a cross-sectional study—although this was a prospective study, mucosal inflammation was assessed at the same time as the colonoscopic diagnosis of diverticulosis, which was likely already present for years. Studies are needed to measure markers of mucosal inflammation before the development of diverticulosis, and to determine whether low-grade mucosal inflammation might eventually lead to diverticulosis and chronic gastrointestinal symptoms. It is also important to identify other possible causes of diverticulosis.
Ma and Chan write that there is still a possibility that a subgroup of patients with symptomatic uncomplicated diverticular disease have subclinical inflammation, which might be uncovered by studies of larger populations or studies comparing levels of inflammation between patients with vs without symptoms.
However, the findings of Peery et al contradict the hypothesis that low-grade inflammation is an etiologic factor for or a consequence of chronic diverticular disease. Further studies are needed before anti-inflammatory agents can be used to treat gastrointestinal symptoms in patients with diverticulosis.