Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways

Cell. 2017 Jun 29;170(1):185-198.e16. doi: 10.1016/j.cell.2017.05.034. Epub 2017 Jun 22.


Dietary, microbial, and inflammatory factors modulate the gut-brain axis and influence physiological processes ranging from metabolism to cognition. The gut epithelium is a principal site for detecting such agents, but precisely how it communicates with neural elements is poorly understood. Serotonergic enterochromaffin (EC) cells are proposed to fulfill this role by acting as chemosensors, but understanding how these rare and unique cell types transduce chemosensory information to the nervous system has been hampered by their paucity and inaccessibility to single-cell measurements. Here, we circumvent this limitation by exploiting cultured intestinal organoids together with single-cell measurements to elucidate intrinsic biophysical, pharmacological, and genetic properties of EC cells. We show that EC cells express specific chemosensory receptors, are electrically excitable, and modulate serotonin-sensitive primary afferent nerve fibers via synaptic connections, enabling them to detect and transduce environmental, metabolic, and homeostatic information from the gut directly to the nervous system.

Keywords: chemosensation; enterochromaffin cell; gastrointestinal physiology; inflammatory bowel disease; intestinal organoid; microbial metabolites; neurogastroenterology; nociception; sensory transduction; visceral pain.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium Channels / metabolism
  • Catecholamines / metabolism
  • Chemoreceptor Cells / metabolism*
  • Enterochromaffin Cells / metabolism*
  • Gastrointestinal Tract / cytology*
  • Gene Expression Profiling
  • Humans
  • Irritable Bowel Syndrome / pathology
  • Mice
  • Nerve Fibers / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways*
  • Receptors, Odorant / metabolism
  • Receptors, Serotonin, 5-HT3 / metabolism
  • Serotonin / metabolism
  • Signal Transduction
  • Synapses / metabolism
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / metabolism


  • Calcium Channels
  • Catecholamines
  • Nerve Tissue Proteins
  • Olfr558 protein, mouse
  • Receptors, Odorant
  • Receptors, Serotonin, 5-HT3
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels
  • Serotonin