Review article: nitric oxide (NO) from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis

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To cite this article: W. E. W. ROEDIGER Review article: nitric oxide (NO) from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis Alimentary Pharmacology & Therapeutics (OnlineAccepted Articles). doi:10.1111/j.1365-2036.2008.03612.x

Review Article

Review article: nitric oxide (NO) from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis

W. E. W. ROEDIGER

Associate ProfessorUniversity of Adelaide Department of SurgeryThe Queen HospitalWoodville, South Australia 5011Australia

Correspondence to:Associate Professor W.E.W. Roediger,University of Adelaide Department of SurgeryThe Queen HospitalWoodville, South Australia 5011AustraliaE-mail: bill.roediger@...

Summary

Background Factors initiating human ulcerative colitis (UC) are unknown. Dysbiosis of bacteria has been proposed to initiate UC but to date neither the nature of the dysbiosis nor mucosal breakdown has been explained.

Aim To assess whether a dysbiosis of anaerobic nitrate respiration could explain the microscopic, biochemical and functional changes observed in colonocytes of ulcerative colitis.

Results Anaerobic nitrate respiration yields nitrite, nitric oxide (NO) and nitrous oxide. Colonic bacteria produce NO and UC in remission has a higher luminal NO level than control cases. NO with sulphide but not NO alone impairs lipid and protein synthesis explaining the membrane, tight junctional, ion channel and β-oxidation changes observed in colonocytes of UC. The observations complement therapeutic mechanisms of those probiotics, prebiotics and antibiotics useful in treating UC.

Conclusions The prolonged production of bacterial NO with sulphide can explain the initiation and barrier breakdown which is central to the pathogenesis of UC. Therapies to alter bacterial nitrate respiration and NO production need to evolve. The production of NO by colonic bacteria and that of the mucosa need to be separated to pinpoint the sequential nature of NO damage in UC.