TY - JOUR
T1 - Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways
AU - Bellono, Nicholas
AU - Bayrer, James
AU - Leitch, Duncan
AU - Castro, Joel
AU - Zhang, Chuchu
AU - O'Donnell, Tracey
AU - Brierley, Stuart
AU - Ingraham, Holly
AU - Julius, David
PY - 2017/6/29
Y1 - 2017/6/29
N2 - 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.
AB - 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.
KW - chemosensation
KW - enterochromaffin cell
KW - gastrointestinal physiology
KW - inflammatory bowel disease
KW - intestinal organoid
KW - microbial metabolites
KW - neurogastroenterology
KW - nociception
KW - sensory transduction
KW - visceral pain
UR - http://www.scopus.com/inward/record.url?scp=85021163248&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2017.05.034
DO - 10.1016/j.cell.2017.05.034
M3 - Article
SN - 0092-8674
VL - 170
SP - 185
EP - 198
JO - Cell
JF - Cell
IS - 1
ER -