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 the 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.