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.

Our gut communicates directly with the brain, altering our eating habits, says new study.

Your sense of taste may or may not be able to identify the difference between natural sugar and substitutes like Splenda, but cells in your intestines can and do tell the difference. In milliseconds, they can transmit the information to your brain.

Not long after the sweet taste receptor was discovered in the mouths of mice 20 years ago, scientists tried to eliminate those taste buds. Even without a sense of taste, mice were able to detect and prefer natural sugar to artificial sweetener, which shocked them.

According to study undertaken by Diego Bohórquez, an associate professor of medicine and neurobiology at Duke University School of Medicine, the answer to this conundrum lies far deeper down in the digestive canal, at the top end of the gut immediately after the stomach.

In a paper published today in Nature Neuroscience, “we’ve identified the cells that make us eat sugar, and they are in the gut,” said the professor.

Sugar injected directly into the lower intestine or colon has a different effect. According to him, the sensing cells are located in the upper regions of the gut.

Following the discovery of a gut cell known as the neuropod cell, Bohórquez and his research team have been exploring this cell’s important role as a link between what happens inside the gut and how it affects the brain. He claims that the gut communicates directly with the brain, altering our eating habits. In the long run, these discoveries could lead to whole new approaches to disease treatment.

Specialized neuropod cells, also known as enteroendrocrine cells because of their ability to produce hormones, can communicate with neurons via fast synaptic connections and are found throughout the upper gut lining. The Bohórquez research team discovered that, in addition to releasing relatively slow-acting hormone signals, these cells also produce fast-acting neurotransmitter signals that reach the vagus nerve and then the brain in milliseconds. 

Neuropods, like taste buds in the tongue or retinal cone cells in the eye that let us see colors, are sensory cells of the nervous system, according to Bohórquez’s recent findings.

“These cells work just like the retinal cone cells that that are able to sense the wavelength of light,” Bohórquez added. “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.’”

The researchers demonstrated in a single experiment that real sugar triggered individual neuropod cells to release glutamate as a neurotransmitter, using lab-grown organoids from mouse and human cells to imitate the small intestine and duodenum (upper gut). ATP, a distinct neurotransmitter, was released when artificial sugar was consumed.

To test if signals from the gut drove the animal’s choice for real sugar, the researchers used optogenetics to turn on and off neuropod cells in a live mouse. The optogenetic experiment was made possible by a novel flexible waveguide fiber developed by MIT scientists. In a living animal, this flexible fiber transmits light throughout the stomach, triggering a genetic response that silences the neuropod cells. With their neuropod cells turned off, the animal didn’t show a clear preference for real sugar any more than it did before.

“We trust our gut with the food we eat,” Bohórquez said. “Sugar has both taste and nutritive 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. “We hope to target this circuit to treat diseases we see every day in the clinic.” 

In future work, Bohórquez said he will be showing how these cells also recognize other macronutrients.

“We always talk about ‘a gut sense,’ and say things like ‘trust your gut,’ well, there’s something to this,” Bohórquez said.

“We can change a mouse’s behavior from the gut,” Bohórquez said, which gives him great hope for new therapies targeting the gut.

Source: 10.1038/s41593-021-00982-7 

Image Credit: Getty

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