Study identifies rare cells as sensors in gut for nervous system

SAN FRANCISCO, June 29 (Xinhua) -- A new study led by University of California, San Francisco, researchers indicates that specialized cells in the gut are able to sense potentially noxious chemicals and trigger electrical impulses in nearby nerve fibers.

Using gut-mimicking "organoids" grown from mouse stem cells, the researchers showed how cells in the intestinal lining called enterochromaffin (EC) cells alert the nervous system to signs of trouble in the gut, from bacterial products to inflammatory food molecules.

The authors of the new study, published online in a recent issue of Cell, said that understanding the role of EC cells in how the gut reacts, and overreacts, to chemical irritants could provide new approaches for treating gastrointestinal disorders such as irritable bowel syndrome (IBS).

With over 100 times the surface area of our skin, the gut is the body's largest surface exposed to external substances. Though EC cells make up only one percent of the gut's lining, they produce 90 percent of the body's serotonin, a key signaling molecule, so researchers have long been curious about their functions.

Best known for mediating mood through its actions in the brain, Serotonin has a different role in the gut, where it is involved in gut contractions and gastric discomfort.

EC cells are interspersed among other cells that make up the lining of the intestinal tract, on the surface of tiny, fingerlike structures called villi that project into the gut's inside space. Within the villi, underneath the EC cells and other cells, are nerve fibers which sense the movement and contents of the gut and contribute to intestinal pain and discomfort. But precisely how these nerve fibers communicate with EC cells has been unclear.

In their study, the researchers showed that EC cells integrate information about chemical irritants, bacterial compounds, and stress hormones in the gut, then use serotonin to pass that information on to the neighboring nerve cells, from which electrical impulses may travel throughout the gut's nervous system and ultimately to the brain.

"There are so few of these cells, but they seem so powerful," Holly Ingraham, a UCSF professor of cellular and molecular pharmacology and co-senior author of the new paper, was quoted as saying in a news release. "People are very interested in understanding what these cells do with all that serotonin."

The team tested the cells' reactions to dozens of different molecules and found that three classes of molecules caused a change in voltage across the cell's membranes. Intriguingly, the three types of molecules that triggered EC cells - bacterial byproducts called volatile fatty acids; a class of hormones called catecholamines that can signal stress in the gut; and a dietary irritant called AITC, which is responsible for garlic's pungent flavor - have all previously been linked to IBS.

"These cells are sensors, like a window looking into the contents of the gut," said James Bayrer, an assistant professor of pediatrics at UCSF and one of the lead authors of the paper.