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

Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways.

Author information

1
Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
2
Department of Pediatrics, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
3
Visceral Pain Group, Flinders University, Bedford Park, SA 5042, Australia; Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, SA 5000, Australia.
4
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: holly.ingraham@ucsf.edu.
5
Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: david.julius@ucsf.edu.

Abstract

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

PMID:
28648659
PMCID:
PMC5839326
DOI:
10.1016/j.cell.2017.05.034
[Indexed for MEDLINE]
Free PMC Article

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