Communication between the gut and brain is thought to control a cornucopia of systems within the body. The gut-brain information highway, also known as the gut-brain axis, is regulated by dietary, microbial, and inflammatory factors to control everything from metabolism to cognition within the host. The gut epithelium is a principal site for detecting such agents, however, precisely how it communicates with neural elements is poorly understood. Now, a study from researchers at UC San Francisco identifies specialized cells, known as enterochromaffin (EC) cells, in the gut able to sense potentially noxious chemicals and trigger electrical impulses in nearby nerve fibers. The team states understanding the role of EC cells in how the gut reacts to chemical irritants could provide new approaches for treating gastrointestinal disorders such as irritable bowel syndrome (IBS). The study is published in the journal Cell.
Previous studies show 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. EC cells are interspersed among other cells on the surface of tiny, fingerlike structures called villi projecting into the gut’s interior making up the lining of the intestinal tract. Within the villi, underneath the EC cells and other cells, are nerve fibers sensing the movement and contents of the gut, contributing to intestinal pain and discomfort. However, precisely how these nerve fibers communicate with EC cells is unclear. The current study utilizes gut-mimicking organoids grown from mouse stem cells to show how EC cells in the intestinal lining alert the nervous system to signs of trouble in the gut.
The current study shows EC cells express excitable chemosensory receptors modulating serotonin-sensitive nerve fibers via synaptic connections, enabling them to communicate with the nervous system. Results show EC cells integrate information about chemical irritants, bacterial compounds, and stress hormones in the gut. Data findings show the EC cells then use serotonin to pass the information on to the neighboring nerve cells, whose electrical impulses travel throughout the gut’s nervous system and ultimately to the brain.
The lab tested the EC cells’ reactions to dozens of different molecules and found three classes of molecules that caused a change in voltage across the cell’s membranes. The group observed the three types of molecules triggering EC cells were fatty acids, a class of hormones known as catecholamines, and a dietary irritant called AITC, all of which have been linked to IBS. They go on to explain when the EC cells are excited by any of these molecules, they release serotonin into synapses with the nearby nerve fibers, triggering electrical impulses, indicating the signal can move quickly throughout the gut.
The team surmises their study gives the global medical community a rigorous handle on exactly how the gut talks to the nervous system via cells behaving like neuronal colonies. For the future, the researchers state they now plan to study EC cells in organoids grown from human cells.
Source: UC San Francisco
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