Your taste buds may or may not be able to distinguish real sugar from a sugar substitute, but there are cells in your intestines that can and do distinguish between the two sweet solutions. And they can communicate the difference to your brain in milliseconds.
Shortly after identifying the sweet taste receptor in the mouths of mice 20 years ago, scientists attempted to knock out those taste buds. But they were surprised to find that mice could still discern and prefer natural sugar over artificial sweetener, even without a sense of taste.
The answer to this riddle lies much lower in the digestive tract, at the upper end of the intestine just past the stomach, according to research led by Diego Bohórquez, associate professor of medicine and neurobiology at Duke University School. of Medicine.
In an article published on January 13 in Natural neuroscience, “we’ve identified the cells that make us eat sugar, and they’re in the gut,” Bohórquez said. Infusing sugar directly into the lower intestine or colon does not have the same effect. The sensing cells are found in the upper part of the intestine, he said.
After discovering a gut cell called a neuropod cell, Bohórquez and his research team pursued the cell’s critical role as a link between what’s inside the gut and its influence in the brain. The gut, he argues, speaks directly to the brain, altering our eating behavior. And in the long run, these discoveries could lead to whole new ways to treat disease.
Originally called enteroendrocrine cells because of their ability to secrete hormones, specialized neuropod cells can communicate with neurons through fast synaptic connections and are distributed throughout the lining of the upper intestine. In addition to producing relatively slow-acting hormonal signals, Bohórquez’s research team showed that these cells also produce fast-acting neurotransmitter signals that reach the vagus nerve and then the brain within milliseconds.
Bohórquez said his group’s latest findings further show that neuropods are sensory cells in the nervous system, much like the taste buds in the tongue or the retinal cone cells in the eye that help us see colors.
“These cells function exactly like retinal cone cells that are able to sense the wavelength of light,” Bohórquez said. “They detect traces of sugar relative to the sweetener, and then they release different neurotransmitters that enter different vagus nerve cells, and eventually the animal knows ‘it’s sugar’ or ‘it’s sweetener “.”
Using organoids grown in the lab from mouse and human cells to represent the small intestine and duodenum (upper intestine), researchers showed in a small experiment that real sugar stimulated individual neuropod cells to release glutamate. as a neurotransmitter. The artificial sugar triggered the release of a different neurotransmitter, ATP.
Using a technique called optogenetics, scientists were then able to switch neuropod cells on and off in the gut of a live mouse to show if the animal’s preference for real sugar was driven by signals from the gut. . The key enabling technology for the optogenetic work was a new flexible waveguide fiber developed by scientists at MIT. This flexible fiber delivers light throughout the gut of a living animal to trigger a genetic response that silenced neuropod cells. With their neuropod cells turned off, the animal no longer showed a clear preference for real sugar.
“We trust our instincts for the food we eat,” Bohórquez said. “Sugar has both taste and nutritional value and the gut is able to identify both.”
“Many people struggle with sugar cravings, and now we have a better understanding of how the gut senses sugars (and why artificial sweeteners don’t curb those cravings),” said co-first author Kelly Buchanan, a Duke University alum. School of Medicine student who is now an internal medicine resident at Massachusetts General Hospital. “We hope to target this circuit to treat diseases that we see every day in the clinic.”
In future work, Bohórquez said he will show how these cells also recognize other macronutrients. “We always talk about ‘instinct’ and say things like ‘trust your instincts’, well, there’s something to that,” Bohórquez said.
“We can change a mouse’s behavior from the gut,” Bohórquez said, giving him great hope for new therapies targeting the gut.
Support for this study came from the National Institutes of Health (R21 AT010818, DP2 MH122402, R01 DK131112), Howard Hughes Medical Institute, Hartwell Foundation, and MIT McGovern Institute.
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Material provided by duke university. Original written by Karl Leif Bates. Note: Content may be edited for style and length.