Distribution and activity of nitrate and nitrite reductases in the microbiota of the human intestinal tract

The human intestinal microbiota plays a vital role in health. One of the most protective benefits is the bacterial nitrogen metabolism of gut bacteria, which reduces nitrate (NO₃ ^-) and nitrite (NO₂ ^-) to ammonia or nitric oxide, preventing the formation of carcinogenic nitrosamines. In this study, we shed light on the gut bacterial NO₂ ^-/NO₃ ^- degradation, its efficacy, and the effects on the steady-state NO₂ ^- concentration in the human colon. Highly abundant gut bacteria that represent the most prominent phyla were analyzed for their potential to reduce NO₂ ^- or NO₃ ^-. Escherichia coli showed the greatest efficiency, which indicates a key role in the detoxification and prevention of nitrosamine formation. Species of the genera Bacteroides and Phocaeicola also contributed to NO₂ ^- reduction due to their high abundance. The total activity of stool samples was about 620 μmol NO₂ ^- h^-1, indicating that NO₂ ^- concentration in the human stool should be very low. We also show that bacterial NO₂ ^- reduction is necessary to allow NO₂ ^--sensitive microorganisms to colonize the intestine, preventing a pathological shift in the composition of the intestinal microbiota. The results illustrate that the gut microbiota plays a central role in NO₂ ^- detoxification, ensuring microbiota integrity and potentially preventing nitrosamine formation and gut-associated cancers.