Cells involved in gut-brain communication identified!

Cells involved in gut-brain communication identified!


Specialized cells in the gut sense potentially noxious chemicals and trigger electrical impulses in nearby nerve fibers, according to a new study. "These cells are sensors, like a window looking into the contents of the gut," said one of the lead authors of the paper.

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 in 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 scientists have long been curious about their functions. Serotonin is best known for mediating mood through its actions in the brain, but it has a very 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 new 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.

"People had suspected such a role for EC cells before, but this study is exciting because for the first time it gives us a rigorous handle on exactly how the gut talks to the nervous system," said study's other senior author.

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 (including dopamine, epinephrine and norepinephrine) 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.

When the EC cells are excited by any of these molecules, they release serotonin into synapses with the nearby nerve fibers, acting much like other sensory organs, from taste buds to odor receptors. In tissue samples taken from mice, the team showed that this serotonin release triggered electrical impulses in nerve fibers, indicating the signal could move quickly throughout the gut.

The intestines are unique among our organs in that many of the nerve signals that control them come not from the brain but from a network of nerves within the gut sometimes called "the second brain," which helps carry out much of the organ's routine contractions and digestive activities without the intervention of the brain itself.

The team thinks the nerve signals that originate with the EC cells can affect both networks, causing involuntary gut contractions or, if the signals reach the brain, what Ingraham described as a "gut ache."
"Just like when we taste something foul and we try to get rid of it" through gagging, the gut may react to the foul "taste" of bacterial or irritating molecules by trying to push them out the other end, said the author. "This could be a way of the gut sensing which populations of bacteria are around."

The next step, said the researchers, is to study EC cells in organoids grown from human cells. Because mice and humans have different diets, our EC cells could be sensitive to entirely different molecules.

https://www.ucsf.edu/news/2017/06/407506/rare-cells-are-window-gut-nervous-system

http://www.cell.com/cell/fulltext/S0092-8674(17)30595-0

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