Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways

Nicholas Bellono, James Bayrer, Duncan Leitch, Joel Castro, Chuchu Zhang, Tracey O'Donnell, Stuart Brierley, Holly Ingraham, David Julius

    Research output: Contribution to journalArticle

    192 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)185-198
    Number of pages14
    JournalCell
    Volume170
    Issue number1
    DOIs
    Publication statusPublished - 2017

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