Nitric Oxide in the Gastrointestinal Tract: Role of Bacteria

Nitric oxide is produced by numerous cell types along the GI tract where it serves to regulate a variety of physiological processes including gut motility, secretions, mucosal blood flow and immunity. Classically, NO is produced from L-arginine and molecular oxygen by specific enzymes, the NO synthases, but more recently a fundamentally different pathway for NO generation was described. This involves stepwise reduction of the higher nitrogen oxides nitrate and nitrite to form NO. In this process commensal bacterial in the GI tract play a key role. Dietary nitrate (mainly provided for by vegetables) accumulates in saliva and the oral microflora reduces this nitrate to nitrite. Nitrite then enters the stomach where it is reduced to NO by the acid. A picture is now emerging suggesting an important role of entero-salivary circulation of nitrate and serial reduction to NO in regulation of gastric function. Intriguingly, the nitrite that survives gastric passage is absorbed and can later recycle to NO in blood and tissues via several enzymatic as well as non-enzymatic pathways. Such systemic NO generation is likely involved in regulation of cardiovascular function and tissue homeostasis, especially in response to ischemia and hypoxia.