Detectable Colonic Nitrite Levels in Inflammatory Bowel Disease – Mucosal or Bacterial Malfunction?

Abstract

In the healthy colon, sodium nitrite stimulates mucosal metabolism of short-chain fatty acids and absorption of ions, both functions that are impaired in the mucosa of patients with ulcerative colitis (UC). To assess the role of nitrite in colonic inflammatory disease, sodium nitrite was measured in rectal dialysate of 49 subjects (18 controls, 23 UC and 8 other colitis). None of the control or quiescent UC patients had measurable levels of nitrite while 78% of patients with acute UC and 38% of patients with other colitis had measurable nitrite levels (acute UC vs. other colitis eχ² = 5.555, p < 0.02). Functional acitivity of the colonic mucosa, judged by bicarbonate output, was impaired in all subjects with measurable nitrite levels in UC. Detection of nitrite in acute colitis suggests impaired oxidation of nitrite to nitrate in the colonic mucosa or impaired luminal reduction of nitrite to NH₄ by bacteria.

The Effect of iNOS Inhibitors and Hyperbaric Oxygen Treatment in a Rat Model of Experimental Colitis

“…There has been extensive focus on NO as a possible etiological factor in the initiation and/or propagation of the inflammatory process in IBD [21,22]. In animal models of colitis, colonic NO generation is increased in association with the development of colitis [7,8,[23][24][25].…”

Nitric oxide: A regulator of mucosal defense and injury

“…Nitrite levels in rectal dialysates from patients with inactive ulcerative colitis (UC) or control patients were not detectable, whereas 78% of the patients with active UC had measurable nitrite levels in rectal dialysates. 79 Lundberg et al 80 found that NO concentrations were more than 100 times higher in colonic luminal gas from patients with active UC than from controls. Increased NO synthase activity has been measured in UC 81,82 and it has been suggested that No may contribute to toxic megacolon.…”

Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity

“…mucus; bacteria; inflammatory bowel diseases; goblet cells SEVERAL FACTORS HAVE BEEN implicated in the pathogenesis of human inflammatory bowel diseases (IBD) including an immunological intolerance to enteric microflora (10 -12, 43), as well as defects in mucosal barrier function (47). Recently, attention has been focused on the overproduction of nitric oxide (NO) in IBD (7,31,46,58). Several studies have identified increased levels of NO in the rectal dialysates (46), in the inflamed mucosa of patients with ulcerative colitis (UC) (3), and in animal models of colitis (26,37,60).…”

“…Recently, attention has been focused on the overproduction of nitric oxide (NO) in IBD (7,31,46,58). Several studies have identified increased levels of NO in the rectal dialysates (46), in the inflamed mucosa of patients with ulcerative colitis (UC) (3), and in animal models of colitis (26,37,60). The increased NO synthase (NOS) activity was identified predominantly as the inducible form of NOS (iNOS) (23).…”