Nitric oxide (NO) is a relatively simple molecule comprising only two atoms. Understanding how this free radical controls an array of complex biological functions provides the platform for much of the research in NO biochemistry and biology. Here, we discuss an updated perspective on how this gas is formed in the body involving a fascinating interplay between the diet, bacteria residing on the tongue, and redox reactions that are regulated by pH and local oxygen tensions. We highlight this as an area primed for novel microbe-targeted therapeutics for controlling NO production and affecting human health and disease.

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