Regulating the ‘mycobiome’

Peptide YY (PYY), a hormone produced by gut endocrine cells that was already known to control appetite, also plays an important role in maintaining the balance of fungi in the digestive system of mammals, according to new research from the University of Chicago.

In a study published this week in Science, researchers found that specialized immune cells in the small intestine called Paneth cells express a form of PYY that prevents the fungus Candida albicans from turning into its more virulent form.

PYY was already known to be produced by endocrine cells in the gut as a hormone that signals satiety, or when an animal has had enough to eat. The new research shows that it also functions as an antimicrobial peptide that selectively allows commensal yeast forms of C. albicans to flourish while keeping its more dangerous forms in check.

Chang and his team didn’t set to explore the fungal side of the gut microbiome, or “mycobiome” as he calls it. Joseph Pierre, PhD, a former postdoctoral scholar in Chang’s lab who is now an Assistant Professor of Nutritional Sciences at the University of Wisconsin-Madison, was studying the enteroendocrine cells in mice that produce PYY when he noticed that it was also present in Paneth cells. These are important immune system defenders in the gut of mammals, secreting several antimicrobial compounds to prevent dangerous bacteria from flourishing.

At first this didn’t make sense, because until then, PYY was only recognized as an appetite hormone. When they tested it against a variety of bacteria, it wasn’t very good at killing them either. But when they ran a computer search for other classes of peptides with a similar structure, they discovered one similar to PYY called magainin 2, which is found on the skin of the African clawed frog. This peptide protects the frogs from infection by both bacteria and fungi, so Chang’s team thought to test PYY’s antifungal properties too. As it turns out, it is not only an effective antifungal agent, but a very specific one as well.