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Neuropod Cells: The Emerging Biology of Gut-Brain Sensory Transduction
Open accessAbstract
Guided by sight, scent, texture, and taste, animals ingest food. Once ingested, it is up to the gut to make sense of the food's nutritional value. Classic sensory systems rely on neuroepithelial circuits to convert stimuli into signals that guide behavior. However, sensation of the gut milieu was thought to be mediated only by the passive release of hormones until the discovery of synapses in enteroendocrine cells. These are gut sensory epithelial cells, and those that form synapses are referred to as neuropod cells. Neuropod cells provide the foundation for the gut to transduce sensory signals from the intestinal milieu to the brain through fast neurotransmission onto neurons, including those of the vagus nerve. These findings have sparked a new field of exploration in sensory neurobiology—that of gut-brain sensory transduction.
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“Enteroendocrine and enterochromaffin cells (ECCs) form close synaptic connections with certain vagal afferent fibers through cell extensions called neuropods [25, 26].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [25]
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BackgroundGut distension evokes rapid neural dynamics in vagal and hindbrain populations of larval zebrafish
Arinel, M., Atkinson, J. A., Matos-Fernández, K. M., Drage, E. P., Hawkyard, M., & Naumann, E. A. (2026) · iScience · doi:10.1016/j.isci.2026.116206 · Cited by 4
“30,33,34 43 While both pathways contribute to gut-brain signaling, the functional consequences of EEC-to-vagal communication are better characterized.”
The atypical adhesion GPCR ADGRA1 controls hippocampal inhibitory circuit function
Tosun, B., Honkanen, K., Orput, E., Kulkarni, S., Bui, D. L. H., & Sando, R. C. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117255 · Cited by 1
Can bacteria control the human brain?
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“[66], located throughout the mucosa of the upper small intestine, are responsible for signaling from the gut to the brain.”
enGLOW 3D microscopy of the enteric nervous system in cleared human and mouse gut
Planchette, A., Gantar, I., Scholler, J., Sobolewski, A., Cabara, Y., Wójcicki, K., Brana, C., Durand, T., Naveilhan, P., Barthet, G., et al. (2026) · Communications Biology · doi:10.1038/s42003-026-09643-6 · Cited by 1
The microbiome and eating disorders: a new framework at the interface of interoception and reward
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Dontamsetti, K. D., Aktar, R., & Peiris, M. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70461 · Cited by 1
“…by the presence of L-cell neuropods, basal extensions containing vesicles that have been shown to juxtapose nerve endings, albeit their prevalence remains debated (Gribble and Reimann 2016; Cao et al. 2024; Gribble and Reimann 2022; Kaelberer et al. 2020; Bohórquez et al. 2011; Liddle 2019).”
Ngoumou, G. B., Schepanski, S. N., Nejati, F., Diedering, A., Cassagnau, N., Beyrow, C., Wicaksono, W. A., Berg, G., & Seifert, G. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1903488 · Cited by 1
Peripheral glia physiology and function
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Role of oral-gut-brain axis in psychiatric and neurological disorders
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“In order to interact with the gut–brain axis, some component of the gut wall, possibly the newly identified neuropod cells discussed earlier [76], has to recognise characteristic semiochemicals that may include dopamine or similar biogenic amines [77].”
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Bayrer, J. R., Castro, J., Venkataraman, A., Touhara, K. K., Rossen, N. D., Morrie, R. D., Hendry, A., Madden, J. S., Braverman, K. N., Schober, G., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.04.486775 · Cited by 1
SEEK to Identify Super Enhancer-Expression Correlated Pairs using Single-cell Multi-omic DataPreprint
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A sensory map of the gastrointestinal tractPreprint
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“3,5 The spatial organization of the molecular components underlying synaptic communication in gut sensory cells is a key area of investigation in the role of a gut sense to drive food choice.”
InfluentialSelf-citationBrain-Resident CD8 + T Cells Regulate Neuronal Activity and Behavior via Interferon-GammaPreprint
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Probiotics and gut-brain axis modulation
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Das Bauchgehirn: neuroanatomische Perspektiven für den Viszeralchirurgen
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InfluentialGut-brain Interactions for the Sucrose Preference
Yamada, S., & Monai, H. (2023) · The Brain & Neural Networks · doi:10.3902/jnns.30.112
Yamada, S., & Monai, H. (2023) · doi:10.3791/65902-v
Recent studies on gut-brain axis and irritable bowel syndrome
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“…synaptic connection of the intestinal lumen to the brainstem (123), thereby allowing regulation of the gut function and communication with the CNS by secreting hormones, which in turn, may activate local sensory nerves or by establishing synaptic communication with enteric glia structures (124).”
BackgroundHuman microbiome and neuro-developmental disorders
Capirig, C. J., Moncayo, J. A., Paramashivaiah, S. H., Khor, S. B., Ong, B. A., & Garcia, C. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15435-5.00010-4
Light-triggered delivery enables brainwide mapping of intragastric glucose sensory dynamics
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Natural gradient Bayesian sampling automatically emerges in canonical cortical circuitsPreprint
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Quantitative descriptive analysis for evaluating the sensory properties of polyphenolsPreprint
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Postoral receptors and alimentary taste: implications for energy intake and appetite
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Metadata
- Authors
- Kaelberer, M. M., Rupprecht, L. E., Liu, W. W., Weng, P., & Bohórquez, D. V.
- Affiliations
- Duke University (US)
- Corresponding author
- Bohórquez, Diego V.
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2020-07-08
- Volume
- 43
- Issue
- 1
- Pages
- 337-353
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- PMC
- PMC7573801
- OpenAlex
- W3007159566
- Cited by
- 236
- References
- 115
- Citations by year
- 2026: 44 · 2025: 58 · 2024: 43 · 2023: 36 · 2022: 26 · 2021: 22 · 2020: 7
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Duke-NUS Medical School
- National Institutes of Health (5r21at010818-02)
- National Institute of Mental Health (DP2MH122402)
- National Institute of General Medical Sciences (T32GM007171)
- National Center for Complementary and Integrative Health (R21-AT010818)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Keywords
- enteroendocrine cells, synapses, neurotransmission, vagus nerve, intestinal hormones
- MeSH terms
- Animals, Brain, Humans, Neurons, Synapses, Vagus Nerve, Signal Transduction, Enteroendocrine Cells
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