"Nature" sub-issue: Surprised!

Your taste buds may not be able to tell the difference between real sugar and sugar substitutes like sugar substitute (sucralose), but there are cells in your gut that can and do differentiate between the two sweeteners

Shortly after the discovery of sweet taste receptors in the mouths of mice 20 years ago, scientists attempted to knock out these taste buds

According to research led by Diego Bohórquez, associate professor of medicine and neurobiology at Duke University School of Medicine, the answer to this puzzle is deeper down the digestive tract, at the upper end of the gut, just after the stomach

In a paper published Jan.

After discovering a type of gut cell called neuropodocyte, Bohórquez and his research team have been studying the cell's key role, which is the link between what's inside the gut and its effect on the brain

Originally known as enteroendocrine cells due to their ability to secrete hormones, specialized neuropodocytes can communicate with neurons through rapid synaptic connections and are distributed throughout the lining of the upper intestine

Bohórquez said his group's latest findings further suggest that neuropods are the sensory cells of the nervous system, like the taste buds on the tongue or the retinal cone cells in the eyes that help us see color

"These cells work like retinal cone cells, sensing wavelengths of light," Bohórquez said.

Using organoids of lab-grown mouse and human cells to represent the small intestine and duodenum (upper intestine), the researchers showed in a small experiment that real sugar stimulates individual neuropodocytes to release glutamate as a neurotransmitters

Using a technique called optogenetics, the scientists were able to switch neuropodocytes on and off in the guts of living mice to show whether the animals' preference for real sugar was driven by gut signals

So many people struggle with their sugar needs, and now we have a better understanding of how the gut feels sugar, and why artificial sweeteners don't curb those cravings

In future work, Bohórquez said he will show how these cells recognize other macronutrients

"We can change the behavior of mice from the gut," says Bohórquez, which gives him great hope for new gut-targeted therapies

Magazine

Nature Neuroscience

DOI

10.
1038/s41593-021-00982-7