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 a new research.
In a study published 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.
“So little is known about what regulates these fungi in our in our microbiome. We know that they're there, but we have no idea what keeps them in a state that provides health benefit to us,” said the senior author of the study. “We now think that this peptide we discovered is actually important for maintaining fungal commensalism in the gut.”
The team didn’t set to explore the fungal side of the gut microbiome, or “mycobiome” as they call it. They were studying the enteroendocrine cells in mice that produce PYY when they 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.
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 generalized infections in the body. When the 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 on the commensal form,” the author said.
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. The senior author 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. But when endocrine cells produce PYY, an enzyme clips off two amino acids to turn it into a hormone that can travel through the bloodstream and tell the brain you’re not hungry. Just like discovering its function from a frog, the author hopes more research on this peptide will turn up more surprises.
“This is an example of the wisdom and beauty of nature that has repurposed a molecule, so it has two different functions,” the author said. “That’s really cool, because this is an efficient way of making the most out of things you already have.”
https://www.science.org/doi/10.1126/science.abq3178
Appetite controlling gut hormone doubles as an immune regulator
- 1,733 views
- Added
Latest News
Multiomics identifies ALS s…
By newseditor
Posted 28 Jun
Reducing age-related inflam…
By newseditor
Posted 28 Jun
Alzheimer's disease symptom…
By newseditor
Posted 27 Jun
Gene-regulatory networks in…
By newseditor
Posted 27 Jun
How apoE influences Aβ aggr…
By newseditor
Posted 26 Jun
Other Top Stories
Small molecule inhibitor targets several proteins to cure for acute…
Read more
Can tumors stop their own spread?
Read more
Six protein kinases may serve as biomarkers for triple negative bre…
Read more
New way to break cancer's vicious cycle
Read more
Mutations and anti-cancer drugs drive cancer growth by blurring gro…
Read more
Protocols
BicemuS: A new tool for neu…
By newseditor
Posted 26 Jun
Deciphering spatial domains…
By newseditor
Posted 23 Jun
High-throughput volumetric…
By newseditor
Posted 21 Jun
Bioengineered human colon o…
By newseditor
Posted 14 Jun
Development of an efficient…
By newseditor
Posted 12 Jun
Publications
Mechanism of chaperone coor…
By newseditor
Posted 29 Jun
TMC7 functions as a suppres…
By newseditor
Posted 29 Jun
Multiomic ALS signatures hi…
By newseditor
Posted 28 Jun
What Is Thyroid Cancer?
By newseditor
Posted 28 Jun
Neurobiological basis of st…
By newseditor
Posted 28 Jun
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar