A gut-brain neural circuit for nutrient sensory transduction
Open accessAbstract
Dissecting the gut-brain axis: It is generally believed that cells in the gut transduce sensory information through the paracrine action of hormones. Kaelberer et al. found that, in addition to the well-described classical paracrine transduction, enteroendocrine cells also form fast, excitatory synapses with vagal afferents (see the Perspective by Hoffman and Lumpkin). This more direct circuit for gut-brain signaling uses glutamate as a neurotransmitter. Thus, sensory cues that stimulate the gut could potentially be manipulated to influence specific brain functions and behavior, including those linked to food choices. Science , this issue p. eaat5236 ; see also p. 1203
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A basolateral cytoplasmic process of L cells, the neuropod, establishes a functional synaptic contact with enteric glia and vagal afferents.
“A basolateral cytoplasmic process of the L cells -the neuropod -was shown to establish a functional synaptic contact with the enteric glia and vagal afferents.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Kaelberer et al., 2018
The sections “A gut-brain neural circuit in a dish” and “Transduction of a sense from gut to brain” report synaptic connections and functional signaling between enteroendocrine cells and vagal nodose neurons. “The neuropod cells” calls these synaptically connected cells neuropod cells. Our copy does not establish a functional synapse with enteric glia or describe the neuropod as a basolateral process of L cells. (LLM, conf=0.88)
Experimental — accuracy not yet measuredVagal afferents form three different types of connections in the gut: intraganglionic laminar endings and intramuscular arrays, terminal axonal endings in the mucosa, and a connection with a subset of enteroendocrine cells (neuropods) which form synapses with vagal neurons.
“Vagal afferents form three different types of connections in the gut: Intraganglionic laminar endings and intramuscular arrays, which both end in muscle wall, as well as terminal axonal endings in the mucosa, and a recently described connection with a subset of enteroendocrine cells, now referred to as neuropods, which form synapses with vagal neurons (Kaelberer et al., 2018).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Kaelberer et al., 2018
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“More recently, it was discovered that enteroendocrine cells synapse with neurons largely originated from both the spinal cord dorsal root ganglia and the vagal nodose ganglia (Kaelberer et al. 2018).”
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- Authors
- Kaelberer, M. M., Buchanan, K. L., Klein, M. E., Barth, B. B., Montoya, M. M., Shen, X., & Bohórquez, D. V.
- Affiliations
- Duke University (US)
- Corresponding author
- Bohórquez, Diego V.
- ORCID
- Venue
- Science
- Published
- 2018-09-21
- Volume
- 361
- Issue
- 6408
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6417812
- OpenAlex
- W2890105461
- Cited by
- 932
- References
- 6
- Citations by year
- 2026: 124 · 2025: 135 · 2024: 139 · 2023: 115 · 2022: 114 · 2021: 113 · 2020: 103 · 2019: 75 · 2018: 10 · 2017: 2
- FWCI
- 71.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (K01 DK-103832, R03 DK114500-01, P30 DK034987 - UNC CGIBD Pilot Award, 1OT2OD023849-01, R35GM122465)
- American Gastroenterological Association (AGA-Elsevier Pilot Research Award)
- The Hartwell Foundation (Individual Biomedical Research Award)
- The Dana Foundation (David Mahoney Neuroimaging Award)
- Defense Sciences Office, DARPA (N66001-15-2-4059)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- gut-brain axis, enteroendocrine cells, vagus nerve, glutamatergic neurotransmission, nutrient sensing, intestinal epithelium, synapses, brainstem, neural circuits, sensory transduction
- MeSH terms
- Animals, Brain Stem, Intestine, Small, Neurons, Synapses, Vagus Nerve, Signal Transduction, Enteroendocrine Cells, Green Fluorescent Proteins, Vesicular Glutamate Transport Protein 1, Mice, Electrophysiological Phenomena
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