How the gut tells sugar from sweetener
Buchanan KL, Rupprecht LE, Kaelberer MM, Sahasrabudhe A, Klein ME, Villalobos JA, Liu WW, Yang A, Gelman J, Park S, Anikeeva P, Bohórquez DV. 2022. The preference for sugar over sweetener depends on a gut sensor cell. Nat Neurosci 25:191–200.
Humans and animals consistently prefer nutritive sugars over non-caloric sweeteners, even when the two taste identical on the tongue. This preference has long puzzled scientists, because it persists even in animals whose sweet taste receptors have been disabled. Something downstream of the mouth must be making the call.
In the intestine, a specialized class of epithelial cells, neuropod cells, synapse directly with vagal neurons and can transmit sensory information to the brain within milliseconds. In the duodenum, these cells are labeled by the hormone cholecystokinin (CCK). We found that CCK-labeled neuropod cells express both sweet taste receptors and sodium-glucose transporters, equipping them to detect and distinguish sugars from sweeteners at the gut surface.
Crucially, the two stimuli do not speak the same language. Sweeteners activate purinergic neurotransmission, while sugars activate glutamatergic neurotransmission, triggering distinct pathways onto the vagus nerve. To test whether these signals actually drive behavior, we developed a flexible fiberoptic waveguide that delivers light directly into the gut lumen of a living mouse, enabling optogenetic control of neuropod cells in real time. When glutamatergic signaling from these cells was silenced, the preference for sugar over sweetener disappeared.
The gut, it turns out, does not just absorb what we eat; it tells the brain what it was.
