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The ability to detect sweetness – whether from sugar or artificial sweeteners – relies on the activity of specialized proteins in the mouth and nasal passages called taste receptors. However, researchers have found that mice that don’t have taste receptors can tell the difference between sugar and artificial sweeteners – and prefer sugar. Findings from a recent study suggest that the capacity to differentiate between sugar and artificial sweeteners is due to the activity of unique cells call neuropods.

Neuropods are enteroendocrine cells – specialized cells that line the gut and sense the presence of food. Located primarily in the duodenum (the upper portion of the intestine), neuropods form synapses (neural connections) with the vagus nerve, a cranial nerve that regulates multiple aspects of the body’s internal functions, including those in the gut. The presence of sugar in the gut causes neuropods to release glutamate, a type of neurotransmitter, facilitating communication via the gut and brain.

The researchers first determined whether neuropods' response to sweetness is specific to sugar, using organoids derived from the intestinal tissues of mice and humans. Organoids are three-dimensional tissue cultures produced from stem cells. They mimic the structure and activity of the organ from which they are derived. The researchers exposed the organoids to sugar or sucralose (an artificial sweetener) and found that sugar promoted the release of glutamate, but sucralose did not.

Then they determined whether the preference for sugar (over artificial sweeteners) arises in the brain or the gut using optogenetics. Optogenetics is a research technique that allows scientists to switch a neuron’s activity on or off using light and genetic engineering. When they turned the neuropod cells in the gut of a living mouse on or off, they found that when the neuropod cells were off, the mouse no longer showed a clear preference for sugar.

These findings suggest that neuropod cells in the gut drive responses to and preferences for sugar. They may further explain why artificial sweeteners often don’t curb the desire (or craving) for sugar. Sugar is ubiquitous in the Western diet and is especially abundant in sugar-sweetened beverages. Learn about the health effects of consuming sugar-sweetened beverages in our overview article.

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