Researchers at the University of Chicago have discovered a gut endocrine cell produced hormone known as peptide YY (PYY) is likely to have an important role keeping the balance of fungi in the digestive system.
When an endocrine cell produces PYY, an enzyme clips off two amino acids to turn into a hormone that can travel through the bloodstream and tell the brain you’re not hungry.
In a study published this week in Science, researchers found that specialised 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.
This is a unique example of an ‘innate’ antimicrobial peptide secreted by Paneth cells that specifically kills the virulent form of this fungi
- Eugene B. Chang, MD, author of the study
“So little is known about what regulates these fungi in our microbiome. We know that they're there, but we have no idea what keeps them in a state that provides health benefits to us,” said Eugene B. Chang, MD, Martin Boyer Professor of Medicine at the University of Chicago and senior author of the study. “We now think that this peptide we discovered is actually important for maintaining fungal commensalism in the gut.”
Regulating the ‘mycobiome’
C. albicans is a yeast that typically grows in small amounts in the mouth, on the skin, and in the intestines. The basic yeast form is commensal, or coexists peacefully in the body, but given the right conditions it transforms into what are called hyphae that branch out to form biofilms. When too much grows, it causes thrush, an infection in the mouth and throat, vaginal yeast infections, or more serious generalised infections in the body. When Chang’s team tested PYY against both forms of the fungus, it effectively prevented growth and killed the more dangerous hyphae while sparing the commensal Candida yeast.
“This is a unique example of an ‘innate’ antimicrobial peptide secreted by Paneth cells that specifically kills the virulent form of this fungi and has no effect on the commensal form,” Chang said.
Making the most out of your molecules
While PYY could be useful as a tool to combat fungal infections, its newly discovered function may play a role in digestive diseases as well. Patients with Crohn’s disease of the ileum, the last portion of the small intestine, often have dysfunctional Paneth cells. Chang said it’s possible that this dysfunction, and lack of PYY, could create an environment for fungi to overgrow and trigger the onset of disease.
The full, unmodified version of PYY has 36 amino acids, and when Paneth cells secrete it into the gut it’s an effective antifungal peptide.