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

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.

Altered tissue metabolites correlate with microbial dysbiosis in colorectal adenomas.

Several studies have linked bacterial dysbiosis with elevated risk of colorectal adenomas and cancer. However, the functional implications of gut dysbiosis remain unclear. Gut bacteria contribute to nutrient metabolism and produce small molecules termed the "metabolome", which may contribute to the development of neoplasia in the large bowel. We assessed the metabolome in normal rectal mucosal biopsies of 15 subjects with colorectal adenomas and 15 nonadenoma controls by liquid chromatography and gas chromatography time-of-flight mass spectrometry. Quantitative real-time PCR was used to measure abundances of specific bacterial taxa. We identified a total of 274 metabolites. Discriminant analysis suggested a separation of metabolomic profiles between adenoma cases and nonadenoma controls. Twenty-three metabolites contributed to the separation, notably an increase in adenoma cases of the inflammatory metabolite prostaglandin E2 and a decrease in antioxidant-related metabolites 5-oxoproline and diketogulonic acid. Pathway analysis suggested that differential metabolites were significantly related to cancer, inflammatory response, carbohydrate metabolism, and GI disease pathways. Abundances of six bacterial taxa assayed were increased in cases. The 23 differential metabolites demonstrated correlations with bacteria that were different between cases and controls. These findings suggest that metabolic products of bacteria may be responsible for the development of colorectal adenomas and CRC.