Buchanan · Nature neuroscience 2022 · preclinical animal experiment with optogenetic manipulation · n=?

The preference for sugar over sweetener depends on a gut sensor cell.

Cited 189 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Animal and mechanistic laboratory study with no human data

PubMed 35027761 · doi:10.1038/s41593-021-00982-7 · record verified 2026-08-26

What was done

The authors investigated how intestinal sensor cells distinguish caloric sugars from non-caloric sweeteners and guide behavioral preference in mice. They examined cholecystokinin (CCK)-labeled duodenal neuropod cells that synapse with vagal neurons, testing receptor involvement (sweet taste receptors and sodium-glucose transporters) and identifying downstream neurotransmitter pathways. To evaluate behavioral causality, they developed an in vivo gut-luminal optogenetics approach using flexible fiberoptics.

What was found

Duodenal neuropod cells differentiated between sugars and non-caloric sweeteners: sweeteners activated purinergic neurotransmission, whereas nutritive sugars triggered glutamatergic neurotransmission to the vagus nerve. In behavioral tests, preference for sugar over non-caloric sweetener in mice depended on glutamatergic signaling from these neuropod cells. The abstract reports no numerical values.

Why it matters

This study reveals a direct gut-to-brain sensory mechanism by which specialized intestinal cells rapidly discriminate caloric nutrients from non-nutritive substitutes to guide dietary preferences.

Limits

This is an animal study in mice; direct translation to human physiology and feeding behavior requires validation. The abstract lacks sample sizes, statistical measures, and exact effect sizes.

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