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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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“Their unique profile aligns with recently identified neuropod cells that link the gut and central nervous system through both endocrine hormones and synaptic neurotransmission (25, 26, 32).”
Id2 GABAergic interneurons comprise a neglected fourth major group of cortical inhibitory cells
Machold, R. P., Dellal, S. S., Valero, M., Zurita, H., Kruglikov, I., Meng, J. H., Hanson, J. L., Hashikawa, Y., Schuman, B., Buzsáki, G., et al. (2023) · eLife · doi:10.7554/elife.85893 · Cited by 24
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Emanuel, E., Arifuzzaman, M., & Artis, D. (2024) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2024.02.004 · Cited by 26
Calcium-permeable AMPA receptors govern PV neuron feature selectivity
Hong, I., Kim, J., Hainmueller, T., Kim, D. W., Keijser, J., Johnson, R. C., Park, S. H., Limjunyawong, N., Yang, Z., Cheon, D., et al. (2024) · Nature · doi:10.1038/s41586-024-08027-2 · Cited by 26
Probiotics and Prebiotics in the Treatment of Autism Spectrum Disorder: A Narrative Review
Zhang, S., Han, F., Wang, Q., & Fan, F. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2301020 · Cited by 29
Avalos, B., Argueta, D. A., Perez, P. A., Wiley, M. B., Wood, C. P., & DiPatrizio, N. V. (2020) · Nutrients · doi:10.3390/nu12092874 · Cited by 25
“, neuropods) in the mouse intestinal epithelium that form functional synapses with afferent vagal fibers [33].”
BackgroundMiles, J., Townend, S., Milonaitytė, D., Smith, W., Hodge, F., Westhead, D. R., & van Oosten‐Hawle, P. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3001605 · Cited by 25
Mechanisms of experience-dependent place-cell referencing in hippocampal area CA1
Qian, F. K., Li, Y., & Magee, J. C. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01930-5 · Cited by 27
James, D. M., Davidson, E. A., Yanes, J. A., Moshiree, B., & Dallman, J. E. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.662916 · Cited by 25
Obesity‐ and diet‐induced plasticity in systems that control eating and energy balance
Ferrario, C. R., Muenzberg, H., Rinaman, L., Betley, J. N., Borgland, S. L., Dus, M., Fadool, D. A., Medler, K. F., Morton, G. J., Sandoval, D. A., et al. (2024) · Obesity · doi:10.1002/oby.24060 · Cited by 24
“EE cells (including neu-ropods) also express microbial recognition receptors, making them well-equipped to sense diet-induced changes in the gut microbiome, such as those that occur during exposure to obesogenic diets [125, 127].”
Getting closer to modeling the gut-brain axis using induced pluripotent stem cells
Hall, V. J., & Bendtsen, K. M. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1146062 · Cited by 21
“A relevant new research area within sensory neurobiology has emerged, namely the field of gut-brain sensory transduction of stimuli for the brain to guide behavior, such as exercise (Kaelberer et al., 2020; Dohnalová et al., 2022).”
BackgroundSugar causes obesity and metabolic syndrome in mice independently of sweet taste
Andrés-Hernando, A., Kuwabara, M., Orlicky, D. J., Vandenbeuch, A., Cicerchi, C., Kinnamon, S. C., Finger, T. E., Johnson, R. J., & Lanaspa, M. A. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00529.2019 · Cited by 22
“One candidate for driving the response to caloric sugars is the recently described neuropod cell, which is a gut sensory epithelial cell that resides in the small intestine and signals the brain via the vagus nerve (13).”
BackgroundThe role of the gut microbiota and fecal microbiota transplantation in neuroimmune diseases
Wu, N., Li, X., Ma, H., Zhang, X., Liu, B., Yuan, W., Zheng, Q., & Fan, X. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1108738 · Cited by 22
Bidirectional regulation of the brain–gut–microbiota axis following traumatic brain injury
You, X., Niu, L., Fu, J., Ge, S., Shi, J., Zhang, Y., & Zhuang, P. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00088 · Cited by 23
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Impact of Enteric Nervous Cells on Irritable Bowel Syndrome: Potential Treatment Options
Pastras, P., Aggeletopoulou, I., & Triantos, C. K. (2024) · Microorganisms · doi:10.3390/microorganisms12102036 · Cited by 18
“These hormones affect nerves and enteric glia through paracrine, afferent, and efferent signaling [59–62].”
BackgroundMinding the gut: extending embodied cognition and perception to the gut complex
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Helminth Sensing at the Intestinal Epithelial Barrier—A Taste of Things to Come
Faniyi, A. A., Wijanarko, K. J., Tollitt, J., & Worthington, J. J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01489 · Cited by 18
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The emerging role of the gut microbiome in depression: implications for precision medicine
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Physical Network Constraints Define the Multiplicative Architecture of the Brain’s ConnectomePreprint
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The Role of Livestock Antibiotic Use in Microbiota Dysbiosis and Neuroinflammation
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“A special subtype of enteroendocrine cells, known as neuropod cells, synapse with vagal neurons, enabling rapid signal transmission from the gut to the brain, often using glutamate as a neurotransmitter [104,106].”
The 5-HT-related gut-brain axis in obesity
Jiang, C., Zhan, Q., & Zeng, C. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123171 · Cited by 13
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“It has even been proposed that synapses are formed between enteroendocrine cells and afferent vagal nerve endings [11,12].”
The microbial guardians: Unveiling the role of gut microbiota in shaping neurodegenerative disease
Izzeddine, N. A., Ahmad, K., Bacha, C., Jabbour, M., Najjar, M., Salhab, S., Ghadieh, H. E., Kanaan, A., Azar, S. T., Khattar, Z. A., et al. (2025) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2025.05.014 · Cited by 19
“These cells can exert effects locally on the enteric nervous system or rapidly transmit signals to the brain via the vagus nerve (kaelberer et al., 2018, Kaelberer et al., 2020, Yano et al., 2015) (Fig.”
Incretin receptor agonism rapidly inhibits AgRP neurons to suppress food intake in mice
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“Sucrose, relative to saccharin, recruits different post-oral signals (Buchanan et al., 2022; Kaelberer et al., 2020), which, in turn, may be differentially integrated with 5TG-recruited signals to modulate dopamine responses.”
BackgroundThe Microbiome–Neurodegeneration Interface: Mechanisms, Evidence, and Future Directions
Böckels, L., Alexa, D., Antal, D. C., Gațcan, C., Alecu, C., Kacani, K., Cretu, R. A., Piseru, E.-A., Bîlcu, R. V., & Cuciureanu, D. I. (2026) · Cells · doi:10.3390/cells15020135 · Cited by 13
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Background
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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