PerspectiveNeuroscience

A gut feeling

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Science  21 Sep 2018:
Vol. 361, Issue 6408, pp. 1203-1204
DOI: 10.1126/science.aau9973

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Summary

The anatomist Friedrich S. Merkel predicted in 1880 that sensory systems are composed of epithelial cells and sensory nerves, which together transform environmental cues into neural signals that trigger our rich sensory experiences (1). We now know that this hypothesis mostly holds true for the canonical senses of vision, hearing, taste, and touch. Perhaps surprisingly, the peripheral outposts of these classical sensory systems (eyes, ears, tongue, and skin) are dwarfed by the human body's largest sensory organ—the gut. Enteroendocrine cells, which are rare epithelial cells that decorate the gut lining, have long been suspected to be sensory receptor cells that inform the brain about ingested nutrients (2). Since their description, these cells were assumed to play a role in metabolism and gut physiology by releasing slow-acting peptide hormones that stimulate neurons throughout the gut and in the brain. On page 1219 of this issue, Kaelberer et al. (3) challenge this view by demonstrating that gut enteroendocrine cells locally excite sensory nerves through release of the neurotransmitter glutamate. A recent study of enterochromaffin cells, a subset of enteroendocrine cells, also found that gut signals are transmitted at epithelial-neural synapses through release of the neurotransmitter serotonin (4). Together, these findings overturn a decades-old dogma that enteroendocrine cells signal exclusively through hormones.