Neuropod Cells Help the Gut Sense Sugar

Duke University researchers have identified cells in the gut that make us prefer sugar over sugar substitutes. Their study is published in Nature Neuroscience today.

Having discovered a gut cell called the neuropod cell, Diego Bohórquez with his research team have been pursuing this cell’s critical role as a connection between what’s inside the gut and its influence in the brain. The gut, he argues, talks directly to the brain, changing our eating behavior. 

Originally termed enteroendrocrine cells because of their ability to secrete hormones, specialized neuropod cells can communicate with neurons via rapid synaptic connections and are distributed throughout the lining of the upper gut. In addition to producing relatively slow-acting hormone signals, the Bohórquez research team has shown 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 of the nervous system just like taste buds in the tongue or the retinal cone cells in the eye that help us see colors. “These cells work just like the retinal cone cells that that are able to sense the wavelength of light,” Bohórquez said. “They sense traces of sugar versus sweetener and then they release different neurotransmitters that go into different cells in the vagus nerve, and ultimately, the animal knows ‘this is sugar’ or ‘this is sweetener.’”

Using lab-grown organoids from mouse and human cells to represent the small intestine and duodenum, the researchers showed in a small experiment that real sugar stimulated individual neuropod cells to release glutamate as a neurotransmitter. Artificial sugar triggered the release of a different neurotransmitter, ATP.

Using optogenetics, the scientists were then able to turn the neuropod cells on and off in the gut of a living mouse to show whether the animal’s preference for real sugar was being driven by signals from the gut. The key enabling technology for the optogenetic work was a new flexible waveguide fiber developed by MIT scientists. This flexible fiber delivers light throughout the gut in a living animal to trigger a genetic response that silenced the neuropod cells. With their neuropod cells switched off, the animal no longer showed a clear preference for real sugar.

“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. “We hope to target this circuit to treat diseases we see every day in the clinic.”