Microbe-host interactions: influence of the gut microbiota on the enteric nervous system
Open accessAbstract
The enteric nervous system (ENS), considered a separate branch of the autonomic nervous system, is located throughout the length of the gastrointestinal (GI) tract as a series of interconnected ganglionated plexi. Given the proximity of the intestinal microbiota to the ENS, it is perhaps not surprising that the gut microbiota can influence its development and function. However, these interactions are complex and may be either direct or indirect, often involving signalling initiated by microbe-derived components, metabolites or host-derived intermediaries which subsequently affect enteric nerve excitability and GI function. Individual microbes and strains can differentially influence ENS activity and neurochemistry. In this review we will briefly summarise the role of the microbiota on ENS development, and, in some more detail, explore the mechanisms by which the microbiota can influence ENS activity and function.
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Microbes residing in the gut can activate stress circuits in the CNS through the vagus nerve and sensory neurons of the ENS.
“There is also evidence for signaling between the GM and CNS, since microbes residing in the gut can activate stress circuits in the CNS through the vagus nerve and sensory neurons of the ENS (21, 49–54).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [54]
Activation of pattern recognition receptors including TLRs by microbial associated molecular patterns is a critical interaction.
“One critical interaction involves the activation of pattern recognition receptors (PRRs), including TLRs, by microbial associated molecular patterns (MAMPs) (54).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [54]
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Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications
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Hung, L. Y., & Margolis, K. G. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00857-1 · Cited by 96 · see citing works
The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologists
Lerner, A., Neidhöfer, S., & Matthias, T. (2017) · Microorganisms · doi:10.3390/microorganisms5040066 · Cited by 94 · see citing works
Gut : liver : brain axis: the microbial challenge in the hepatic encephalopathy
Mancini, A., Campagna, F., Amodio, P., & Tuohy, K. M. (2018) · Food & Function · doi:10.1039/c7fo01528c · Cited by 89 · see citing works
Role of gut microbiota-derived signals in the regulation of gastrointestinal motility
Zheng, Z., Tang, J., Hu, Y., & Zhang, W. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.961703 · Cited by 91 · see citing works
The microbiota-gut-brain axis: Focus on the fundamental communication pathways
Bistoletti, M., Bosi, A., Banfi, D., Giaroni, C., & Baj, A. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.08.012 · Cited by 88 · see citing works
The Rice Microbiome: A Model Platform for Crop Holobiome
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Chen, Y., Li, Y., Fan, Y., Chen, S., Chen, L., Chen, Y., & Chen, Y. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2302310 · Cited by 91 · see citing works
Advances in Enteric Neurobiology: The “Brain” in the Gut in Health and Disease
Kulkarni, S., Ganz, J., Bayrer, J. R., Becker, L. S., Bogunovic, M., & Rao, M. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1663-18.2018 · Cited by 83 · see citing works
Gut Microbiota and Bone Health
Quach, D., & Britton, R. A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-66653-2_4 · Cited by 84 · see citing works
Sanchez, J. B., & Kadrofske, M. M. (2019) · Neurogastroenterology & Motility · doi:10.1111/nmo.13569 · Cited by 81 · see citing works
Aktar, R., Parkar, N., Stentz, R., Baumard, L., Parker, A., Goldson, A. J., Brion, A., Carding, S. R., Blackshaw, L. A., & Peiris, M. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1766936 · Cited by 80 · see citing works
Chen, Q., Ren, Y., Lu, J., Bartlett, M., Chen, L., Zhang, Y., Guo, X., & Liu, C. (2017) · Nutrients · doi:10.3390/nu9121341 · Cited by 76 · see citing works
Impact of selected environmental factors on microbiome of the digestive tract of ruminants
Cholewińska, P., Górniak, W., & Wojnarowski, K. (2021) · BMC Veterinary Research · doi:10.1186/s12917-021-02742-y · Cited by 75 · see citing works
Diabetes-induced mechanophysiological changes in the small intestine and colon
Zhao, M., Liao, D., & Zhao, J. (2017) · World Journal of Diabetes · doi:10.4239/wjd.v8.i6.249 · Cited by 75 · see citing works
He, Y., Wang, K., Su, N., Yuan, C., Zhang, N., Hu, X., Fu, Y., & Zhao, F. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.70099 · Cited by 73 · see citing works
Gut, Microbiome, and Brain Regulatory Axis: Relevance to Neurodegenerative and Psychiatric Disorders
Stefano, G. B., Pilonis, N., Ptáček, R., Raboch, J., Vňuková, M., & Kream, R. M. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0589-2 · Cited by 71 · see citing works
Nerves in gastrointestinal cancer: from mechanism to modulations
Vaes, N., Idris, M., Boesmans, W., Alves, M. M., & Melotte, V. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00669-9 · Cited by 68 · see citing works
Lei, W., Cheng, Y., Liu, X., Gao, J., Zhu, Z., Ding, W., Xu, X., Li, Y., Ling, Z., Jiang, R., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1582119 · Cited by 68 · see citing works
Dicks, L. M. T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010038 · Cited by 66 · see citing works
Stress and the gut-brain axis: an inflammatory perspective
Morys, J., Małecki, A., & Nowacka-Chmielewska, M. M. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1415567 · Cited by 77 · see citing works
Ballway, J. W., & Song, B.-J. (2021) · Antioxidants · doi:10.3390/antiox10030384 · Cited by 68 · see citing works
Parathan, P., Wang, Y., Leembruggen, A. J. L., Bornstein, J. C., & Foong, J. P. P. (2019) · Developmental Biology · doi:10.1016/j.ydbio.2019.10.011 · Cited by 64 · see citing works
Functional Bowel Disorders: A Roadmap to Guide the Next Generation of Research
Chang, L., Lorenzo, C. D., Farrugia, G., Hamilton, F. A., Mawe, G. M., Pasricha, P. J., & Wiley, J. W. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.12.010 · Cited by 62 · see citing works
Gut Bacteria and Neuropsychiatric Disorders
Dicks, L. M. T., Hurn, D., & Hermanus, D. (2021) · Microorganisms · doi:10.3390/microorganisms9122583 · Cited by 61 · see citing works
Exploring the microbiome in health and disease
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Li, T., Yan, Q., Wen, Y., Liu, J., Sun, J. G., & Jiang, Z. (2021) · Journal of Dairy Science · doi:10.3168/jds.2020-19449 · Cited by 52 · see citing works
Fakhri, S., Yarmohammadi, A., Yarmohammadi, M., Farzaei, M. H., & Echeverría, J. (2021) · Marine Drugs · doi:10.3390/md19030165 · Cited by 51 · see citing works
Redondo, N., Gheorghe, A., Díaz, L. E., Villavisencio, B., Marcos, A., & Nova, E. (2019) · Nutrients · doi:10.3390/nu11030651 · Cited by 49 · see citing works
Glinert, A., Turjeman, S., Elliott, E., & Koren, O. (2021) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12812 · Cited by 45 · see citing works
Deng, Y., Li, M., Lü, M., Cong, L., Liu, Y., Zhang, B., He, C., Zheng, P., & Yuan, J. (2018) · Beneficial Microbes · doi:10.3920/bm2017.0062 · Cited by 45 · see citing works
Yadav, H., Jaldhi, Bhardwaj, R., Anamika, A., Bakshi, A., Gupta, S., & Maurya, S. K. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122022 · Cited by 46 · see citing works
Bayer, F., Dremova, O., Khuu, M. P., Mammadova, K., Pontarollo, G., Kiouptsi, K., Soshnikova, N. V., May‐Simera, H., Endres, K., & Reinhardt, C. (2021) · Nutrients · doi:10.3390/nu13072198 · Cited by 44 · see citing works
Tyagi, P., Tasleem, M., Prakash, S., & Chouhan, G. (2020) · Food Research International · doi:10.1016/j.foodres.2020.109489 · Cited by 42 · see citing works
Rewiring the Brain Through the Gut: Insights into Microbiota–Nervous System Interactions
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Slykerman, R. F., Davies, N., Vlčková, K., O’Riordan, K. J., Bassett, S. A., Dekker, J., Schellekens, H., Hyland, N. P., Clarke, G. A., & Patterson, E. (2025) · Microbial Biotechnology · doi:10.1111/1751-7915.70079 · Cited by 43 · see citing works
Self-citationGut Microbiota at the Intersection of Alcohol, Brain, and the Liver
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Interleukin-17 acts in the hypothalamus reducing food intake
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Metabolome and microbiome profiling of a stress-sensitive rat model of gut-brain axis dysfunction
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Dietary modulation of gut microbiota for the relief of irritable bowel syndrome
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Making Sense of Quorum Sensing at the Intestinal Mucosal Interface
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Self-citationWithout a bug’s life: Germ-free rodents to interrogate microbiota-gut-neuroimmune interactions
Spichak, S., Guzzetta, K. E., O’Leary, O. F., Clarke, G. A., Dinan, T. G., & Cryan, J. F. (2018) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2019.08.002 · Cited by 28 · see citing works
Self-citationThe Role of Gut Microbiome in Irritable Bowel Syndrome: Implications for Clinical Therapeutics
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Enterochromaffin Cells: Sentinels to Gut Microbiota in Hyperalgesia?
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Regulating the Enteric Nervous System against Obesity in Mice by Electroacupuncture
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Cellular Immune Signal Exchange From Ischemic Stroke to Intestinal Lesions Through Brain-Gut Axis
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Hyaluronan: A Neuroimmune Modulator in the Microbiota-Gut Axis
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Role of sulfidogenic members of the gut microbiota in human disease
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- Authors
- Hyland, N. P., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Corresponding author
- Hyland, Niall P.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 417
- Issue
- 2
- Pages
- 182-187
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W2468315138
- Cited by
- 207
- References
- 51
- Citations by year
- 2026: 11 · 2025: 34 · 2024: 27 · 2023: 16 · 2022: 22 · 2021: 26 · 2020: 18 · 2019: 15 · 2018: 20 · 2017: 15 · 2016: 3
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Board (HRA_POR/2012/32)
- European Commission (613979, FP7-KBBE-2013-7)
- Science Foundation Ireland
- Irish Research Council (EPSPD/2015/52)
- APC Microbiome Institute (SFI/12/RC/2273)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- gut microbiota, enteric nervous system, microbiota-host interactions, gut-brain axis, microbial metabolites, neurochemistry, gastrointestinal function, enteric nervous system development
- MeSH terms
- Gastrointestinal Microbiome, Animals, Germ-Free Life, Humans, Signal Transduction, Enteric Nervous System, Probiotics, Gastrointestinal Tract, Mice, Neurogenesis
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