Enterochromaffin cells are gut chemosensors that couple to sensory neural pathways
Open accessAbstract
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.
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Enterochromaffin cells synthesize more than 90% of serotonin synthesized in vivo.
“Bellon et al. (61) found that enterochromaffin cells synthesize more than 90% of serotonin synthesized in vivo, this being a key neurotransmitter involved in regulation of mood, feeding, sleep, and pain processing (62).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [61]
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- Authors
- Bellono, N. W., Bayrer, J. R., Leitch, D. B., Castro, J., Zhang, C., O’Donnell, T. A., Brierley, S. M., Ingraham, H. A., & Julius, D.
- Affiliations
- University of California, San Francisco (US)
- Flinders University (AU)
- Corresponding author
- Ingraham, Holly A.
- Julius, David
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 170
- Issue
- 1
- Pages
- 185-198.e16
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5839326
- OpenAlex
- W2658508676
- Cited by
- 910
- References
- 63
- Citations by year
- 2026: 99 · 2025: 127 · 2024: 121 · 2023: 94 · 2022: 106 · 2021: 108 · 2020: 84 · 2019: 73 · 2018: 71 · 2017: 27
- FWCI
- 73.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH Institutional Research Service Award (T32HL007731)
- Life Sciences Research Foundation
- Simons Foundation Postdoctoral Fellowship
- NIH (R01 NS081115, R01 NS055299, R01 DK099722, K12 HD072222, K08 DK106577)
- American Diabetes Association (714MI08)
- National Health and Medical Research Council of Australia (APP1083480)
- NHMRC R.D. Wright Biomedical Research (APP1126378)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- enterochromaffin cells, gut-brain axis, chemical sensors, serotonin, intestinal organoids, chemosensory receptors, electrical excitability, synaptic signaling, intestinal epithelium, single-cell transcriptomics
- MeSH terms
- TRPA1 Cation Channel, Amino Acid Sequence, Animals, Base Sequence, Catecholamines, Chemoreceptor Cells, Enterochromaffin Cells, Humans, Nerve Fibers, Nerve Tissue Proteins, Neural Pathways, Serotonin, Synapses, Calcium Channels, Signal Transduction, Receptors, Odorant, Gene Expression Profiling, Gastrointestinal Tract, Irritable Bowel Syndrome, Receptors, Serotonin, 5-HT3, Transient Receptor Potential Channels, Mice
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