A gut-brain neural circuit for nutrient sensory transduction

Science. 2018 Sep 21;361(6408):eaat5236. doi: 10.1126/science.aat5236.


The brain is thought to sense gut stimuli only via the passive release of hormones. This is because no connection has been described between the vagus and the putative gut epithelial sensor cell-the enteroendocrine cell. However, these electrically excitable cells contain several features of epithelial transducers. Using a mouse model, we found that enteroendocrine cells synapse with vagal neurons to transduce gut luminal signals in milliseconds by using glutamate as a neurotransmitter. These synaptically connected enteroendocrine cells are referred to henceforth as neuropod cells. The neuroepithelial circuit they form connects the intestinal lumen to the brainstem in one synapse, opening a physical conduit for the brain to sense gut stimuli with the temporal precision and topographical resolution of a synapse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Stem / physiology*
  • Electrophysiological Phenomena
  • Enteroendocrine Cells / cytology
  • Enteroendocrine Cells / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Intestine, Small / cytology*
  • Intestine, Small / physiology
  • Mice
  • Neurons / cytology
  • Signal Transduction
  • Synapses*
  • Vagus Nerve / physiology
  • Vesicular Glutamate Transport Protein 1 / metabolism


  • Slc17a7 protein, mouse
  • Vesicular Glutamate Transport Protein 1
  • Green Fluorescent Proteins