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Abstract

A pathogenic role of nitric oxide has been suggested in acute and chronic intestinal inflammation. We took the opportunity offered by studies in patients with excluded colon, which represents a model of chronic intestinal inflammation with no exogenous nitrite or nitrate supply, to evaluate the quantity and the quality of nitrate reducers in diversion colitis. Thirty patients (17 men, 13 women, mean age 45 years) having an excluded colon for various reasons were sampled by rectal swabs and compared to 30 healthy controls (11 men, 19 women, mean age 28 years). The percentage of nitrate-reducers among the total count of subcultured bacteria was 46 +/- 41% (mean +/- SD) in patients with diversion colitis as compared to 19 +/- 24% in healthy controls. This difference was significant (P < 0.05) despite great heterogeneity in individual values. In patients with diversion colitis, 75/254 (29.5%) different isolated bacterial strains were nitrate-reducers as compared to 61/294 (21%) (P < 0.05) in controls. Among the 75 nitrate-reducing strains isolated from patients with diversion colitis, 55 were aerobes. Pseudomonas species were only encountered in this population. The predominant group was enterobacteria with a high isolation rate of species belonging to the genera Proteus, Providencia, and Morganella. In healthy controls nitrate-reducing anaerobes were nearly as frequent as aerobes. The most frequent species was Eubacterium lentum, followed by Clostridium perfringens. It could be suggested that nitric oxide synthase might produce a bacterial substrate increasing the growth of bacteria with a high pathogenic potential, creating conditions for chronic inflammation and infection in patients with excluded colon.

Relationship between the Severity of Diversion Colitis and the Composition of Colonic Bacteria: A Prospective Study

“…Ideally, we would have performed PCR analysis for all recognized bacteria, but this approach was not possible in practice because the number of bacteria is nearly infinite. Therefore, we relied on the findings from our culture experiments and previous studies to select the bacteria for PCR analysis 17,19,20. Unfortunately, this strategy also had some limitations: the selection of a standard is ambiguous and dependent on existing information.…”

“…We then used a portion of these samples to perform DNA extraction using a DNA extraction kit (Intron Biotechnology, Seoul, Korea). We selected 11 bacterial genera for polymerase chain reaction (PCR) analysis based on the other previous studies17,19,20 and our preliminary culture experiments as follows: Staphylococcus , Streptococcus , Enterococcus , Enterobacteriaceae , Klebsiella , Pseudomonas , Lactobacillus , Bacteroides , Clostridium , Eubacterium , and Bifidobacterium . Primer sets used in this study are summarized in Table 1.…”

“…Other studies have suggested that oxidative DNA damage and a mutation of p53 can lead to diversion colitis 12-14. Furthermore, the number of nitrate-reducing bacteria, which metabolize nitric oxide and are related to chronic inflammation of colon, are higher in patients with diversion colitis 15-17. However, most of these results were derived from animal studies or reports after empirical treatment, and the exact cause of diversion colitis is still unknown.…”

Nitric Oxide Damage to Colonocytes in Colitis-by-Association: Remote Transfer of Nitric Oxide to the Colon

“…Further support for such a possibility is that nitrate-reducing bacteria pre-dominate in the isolated and defunctioned colon [45]. The detection of nitric oxide in the healthy human rectum in patients with inflammation in the ileum and caecum [46]provides clinical support for the observation of circulatory carriage with transmucosal extraction of nitric oxide into the rectum.…”

“…In ulcerative colitisUC, glutathione levels are depleted [60, 61, 62]which may enhance the damaging effect of nitric oxide in progressive colitis. Consumption of nitric oxide by anaerobic bacteria normally takes place [45, 47]to protect the injurious activity of this molecule.…”