When you take a bite of food, your teeth break-up the food into little pieces that are easier to digest, saliva is secreted that contain amylases to help break down starches, then you swallow, allowing your stomach and gut to do the rest of the work. Now if that food you are eating is contaminated with bacteria, the acid produced by your stomach will kill the microorganisms, preventing disease. Or so you’ve been told.
It makes sense, the low pH of the stomach acid seems to be enough to kill any living thing. If the mucosal lining of your stomach isn’t there then it will start eating away at the tissue, causing ulcers. However, stomach acid alone is not enough to kill some pathogens. Gastric acid needs a little help from its friend, nitric oxide (NO). NO can inhibit or kill pathogens by binding covalently to DNA, proteins, and lipids.
Nitrate from your diet, especially leafy-greens, gets converted to nitrite by the commensal bacteria in the mouth. Nitrite then goes to the stomach to be reduced to NO in the acidic conditions of the stomach. Alternatively, NO can be synthesized from L-arginine, oxygen, and NADPH. NO is found in other parts of the body too. It acts as a neurotransmitter between nerve cells and is a potent vasodilator. Macrophages, monocytes, and neutrophils are armed with NO which it uses to kill off invading pathogens.
Clostridium difficile, or as it is more commonly referred, C-diff, is a serious problem in hospitals; it frequently occurs in patients after antibiotic-treatment. This infection causes severe, and sometimes fatal, diarrhea. Usually inducing complications such as pseudomembranous colitis or toxic megacolon. These complications can lead to perforation of the colon and sepsis, increasing the likelihood of death.
What makes C-diff so difficult to treat, aside from the rise in antibiotic-resistant strains, is that the organism forms spores. These spores are heavily resistant to most stressors. Low pH and gastric acid, is one such environmental stress that C-diff spores can survive. It would seem counter-intuitive that patients on proton-pump inhibitors would have a higher rate of C-diff infections.
Proton-pump inhibitors decrease the amount acid in the stomach. So for an organism that is resistant, why does it matter? It turns out, C-diff spores are sensitive to NO. As mentioned, the stomach acid is responsible for the last step of converting nitrite into nitric oxide. A decrease in stomach acid, in turn, causes a decrease in NO production in the stomach, allowing for C-diff to survive.
Helicobacter pylori is another example of a gastric pathogen that is resistant to the acidic conditions of the stomach. Establishing itself in the stomach can result in the formation of ulcers. However, it too is killed by nitric oxide. Unfortunately for us, H. plyori has ways of getting around the effects of NO by disrupting the NO production of eukaryotic cells.
Gastric acid may get all the credit for sterilizing your food but it’s NO that is the secret weapon. Harnessing the power of NO as an antimicrobial is being explored by scientists.