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Gut feeling: a direct pathway for gut-brain communication

Researchers have identified for the first time a direct line of communication between the gut and the brain that allows for rapid signaling of sensory information about food intake. It has long been known that the stomach and intestines communicate with the brain. However, scientists thought that this exchange of information occurred through a slow diffusion of hormones released by specialized intestinal cells termed “enteroendocrine cells” into the bloodstream upon ingesting nutrients. Recently, a team of investigators wondered if a faster conduit through the nervous system might exist, given that circulating hormones reach their peak several minutes after food is consumed and a person has already had a sense of feeling full.

To determine if a direct neural pathway exists, the researchers used a technique to detect cellular connections in mice with a modified, fluorescently-tagged rabies virus, as rabies spreads through the body via connections between nerve cells (neurons) until it reaches the brain. They introduced this virus into the colons of the mice, and, remarkably, they were able to trace the fluorescent signal as the virus traveled from a novel subtype of intestinal enteroendocrine cell (named neuropod by the authors) all the way to cells in the brainstem, called vagal neurons, indicating the presence of a direct circuit. To recreate the gut-brain connection in the lab, the researchers next grew these gut cells from mice in the same dish as vagal neurons. They saw the neurons’ extensions crawl along the bottom of the dish to connect to the gut cells and begin communicating. Using a technique to measure the speed of the signal, they found that adding a sugar solution to the dish triggered a message to travel between gut and brain cells. The speed of communication was extremely fast—measured in milliseconds, much faster than the blink of an eye. When sugar was added to vagal neurons in the absence of gut cells, there was no measurable signal, suggesting that the message was being sent from the gut cells only in the presence of a food source. Because such rapid communication between the brain and other organs involving the five senses—smell, taste, touch, vision, and hearing—often occurs via a chemical messenger called glutamate, the researchers next investigated if glutamate was also responsible for delivering these fast signals from the gut to the brain. When they blocked the release of glutamate with a chemical agent in a dish containing vagal neurons and gut cells, the messages were silenced, suggesting that glutamate is the chemical messenger responsible for this communication; when they washed away the blocking agent, the signal was recovered. Thus, the researchers had discovered that certain gut cells connect with and speak the language of brain cells in rapid communication.

Taken together, these results lend new meaning to a “gut feeling” as a “sixth sense,” in terms of sensing and rapidly communicating information about the food we eat. Future research could provide insight into whether this gut-brain system relays specific information about nutrients and caloric intake of food.

Kaelberer MM, Buchanan KL, Klein ME, …Bohórquez DV. A gut-brain neural circuit for nutrient sensory transduction. Science. 361: 1219-1227, 2018.

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