The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse
Abstract
Background The role of intestinal microbiota in the development and function of host physiology is of high interest, especially with respect to the nervous system. While strong evidence has accrued that intestinal bacteria alter host nervous system function, mechanisms by which this occurs have remained elusive. For this reason, we have carried out experiments examining the electrophysiological properties of neurons in the myenteric plexus of the enteric nervous system (ENS) in germ-free (GF) mice compared with specific pathogen-free (SPF) control mice and adult germ-free mice that have been conventionalized (CONV-GF) with intestinal bacteria. Methods Segments of jejunum from 8 to 12 week old GF, SPF, and CONV-GF mice were dissected to expose the myenteric plexus. Intracellular recordings in current-clamp mode were made by impaling cells with sharp microelectrodes. Action potential (AP) shapes, firing thresholds, the number of APs fired at 2× threshold, and passive membrane characteristics were measured. Key results In GF mice, excitability was decreased in myenteric afterhyperpolarization (AH) neurons as measured by a lower resting membrane potential and by the number of APs generated at 2× threshold. The post AP slow afterhyperpolarization (sAHP) was prolonged for GF compared with SPF and CONV-GF animals. Passive membrane characteristics were also altered in GF mice by a decrease in input resistance. Conclusions & inferences Here, we report the novel finding that commensal…
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Germ-free status is accompanied by significant alterations in the electrophysiology and characteristic profile of after-hyperpolarization-type enteric neurons (intrinsic primary afferent neurons), reflected as decreased excitability and discharge.
“GF status is accompanied by significant alterations in the electrophysiology and characteristic profile of after-hyperpolarization-type enteric neurons (intrinsic primary afferent neurons) reflected as decreased excitability and discharge (McVey Neufeld et al., 2013)”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as McVey Neufeld et al., 2013
GF animals have decreased basal neural excitability and altered intrinsic primary afferent neuron excitability compared to SPF and conventionally re-colonized GF controls.
“as well as decreased basal neural excitability, as evidenced by an augmented post action potential, as well as altered intrinsic primary afferent neuron excitability, as measured in the form of an enhanced slow afterhyperpolarization, when compared to SPF and conventionally re-colonized GF control animals (McVey Neufeld et al., 2013).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as McVey Neufeld et al., 2013
Network activity of host physiology in myenteric sensory neurons differs greatly in GF mice from conventional and SPF strains.
“Furthermore, network activity of host physiology in myenteric sensory neurons differed greatly in GF mice from conventional and SPF strains in a study examining jejunum intracellular current-clamp recordings (McVey Neufeld et al., 2013), indicating a fundamental shift in synaptic efficacy in the absence of microbiota.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as McVey Neufeld et al., 2013
Cites
Normal gut microbiota modulates brain development and behavior
Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M. L., Forssberg, H., & Pettersson, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010529108 · Cited by 3,228 · see citing works
Brain-gut-microbe communication in health and disease
Grenham, S., Clarke, G., Cryan, J. F., & Dinan, T. G. (2011) · Frontiers in Physiology · doi:10.3389/fphys.2011.00094 · Cited by 952 · see citing works
The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review
Moayyedi, P., Ford, A. C., Talley, N. J., Cremonini, F., Foxx-Orenstein, A. E., Brandt, L. J., & Quigley, E. M. M. (2010) · Gut · doi:10.1136/gut.2008.167270 · Cited by 728 · see citing works
Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice
Verdú, E. F., Bercik, P., Verma-Gandhu, M., Huang, X.-X., Blennerhassett, P., Jackson, W., Mao, Y., Wang, L., Rochat, F., & Collins, S. M. (2006) · Gut · doi:10.1136/gut.2005.066100 · Cited by 448 · see citing works
Self-citationMicrobes and the gut‐brain axis
Bercik, P., Collins, S. M., & Verdu, E. F. (2012) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2012.01906.x · Cited by 417 · see citing works
Jalanka-Tuovinen, J., Salonen, A., Nikkilä, J., Immonen, O., Kekkonen, R., Lahti, L., Palva, A., & de Vos, W. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023035 · Cited by 340 · see citing works
Effects of intestinal microbiota on anxiety-like behavior
Neufeld, K.-A. M., Kang, N., Bienenstock, J., & Foster, J. A. (2011) · Communicative & Integrative Biology · doi:10.4161/cib.15702 · Cited by 311 · see citing works
Self-citation
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015) · Cell · doi:10.1016/j.cell.2015.02.047 · Cited by 3,614 · see citing works
Gut–brain axis: How the microbiome influences anxiety and depression
Foster, J. A., & McVey Neufeld, K.-A. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.01.005 · Cited by 2,460 · see citing works
Self-citationStress & the gut-brain axis: Regulation by the microbiome
Foster, J. A., Rinaman, L., & Cryan, J. F. (2017) · Neurobiology of Stress · doi:10.1016/j.ynstr.2017.03.001 · Cited by 1,150 · see citing works
Self-citationKelly, J. R., Kennedy, P. J., Cryan, J. F., Dinan, T. G., Clarke, G., & Hyland, N. P. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00392 · Cited by 1,110 · see citing works
Psychobiotics and the manipulation of bacteria–gut–brain signals
Sarkar, A., Lehto, S. M., Harty, S., Dinan, T. G., Cryan, J. F., & Burnet, P. W. J. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.09.002 · Cited by 1,068 · see citing works
The microbiota-gut-brain axis: from motility to mood
Margolis, K. G., Cryan, J. F., & Mayer, E. A. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.066 · Cited by 999 · see citing works
Gut microbiome and aging: physiological and mechanistic insights
Nagpal, R., Mainali, R., Ahmadi, S., Wang, S., Singh, R., Kavanagh, K., Kitzman, D. W., Kushugulova, A., Marotta, F., & Yadav, H. (2018) · Nutrition and Healthy Aging · doi:10.3233/nha-170030 · Cited by 670 · see citing works
Luczynski, P., McVey Neufeld, K.-A., Oriach, C. S., Clarke, G., Dinan, T. G., & Cryan, J. F. (2016) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw020 · Cited by 632 · see citing works
Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis
Stilling, R. M., Dinan, T. G., & Cryan, J. F. (2014) · Genes, Brain and Behavior · doi:10.1111/gbb.12109 · Cited by 637 · see citing works
Vagal pathways for microbiome-brain-gut axis communication
Forsythe, P., Bienenstock, J., & Kunze, W. A. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_5 · Cited by 576 · see citing works
Self-citationCollective unconscious: How gut microbes shape human behavior
Dinan, T. G., Stilling, R. M., Stanton, C., & Cryan, J. F. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.02.021 · Cited by 571 · see citing works
De Vadder, F., Grasset, E., Mannerås Holm, L., Karsenty, G., Macpherson, A. J., Olofsson, L. E., & Bäckhed, F. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720017115 · Cited by 566 · see citing works
Autism Spectrum Disorders and the Gut Microbiota
Fattorusso, A., Di Genova, L., Dell’Isola, G., Mencaroni, E., & Esposito, S. (2019) · Nutrients · doi:10.3390/nu11030521 · Cited by 484 · see citing works
The microbiome: stress, health and disease
Moloney, R. D., Desbonnet, L., Clarke, G., Dinan, T. G., & Cryan, J. F. (2014) · Mammalian Genome · doi:10.1007/s00335-013-9488-5 · Cited by 430 · see citing works
Relationship between the gut microbiome and brain function
Mohajeri, M. H., La Fata, G., Steinert, R. E., & Weber, P. (2018) · Nutrition Reviews · doi:10.1093/nutrit/nuy009 · Cited by 376 · see citing works
Microbiota controls the homeostasis of glial cells in the gut lamina propria
Kabouridis, P. S., Lasrado, R., McCallum, S., Chng, S. H., Snippert, H. J., Clevers, H., Pettersson, S., & Pachnis, V. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.037 · Cited by 358 · see citing works
The Impact of Microbiota on Brain and Behavior: Mechanisms & Therapeutic Potential
Borre, Y. E., Moloney, R. D., Clarke, G., Dinan, T. G., & Cryan, J. F. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_17 · Cited by 329 · see citing works
Intestinal microbiota influence the early postnatal development of the enteric nervous system
Collins, J., Borojevic, R., Verdu, E. F., Huizinga, J. D., & Ratcliffe, E. M. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12236 · Cited by 318 · see citing works
Heiss, C. N., & Olofsson, L. E. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12684 · Cited by 304 · see citing works
Microbiota regulation of the mammalian gut-brain axis
Burokas, A., Moloney, R. D., Dinan, T. G., & Cryan, J. F. (2015) · Advances in applied microbiology · doi:10.1016/bs.aambs.2015.02.001 · Cited by 300 · see citing works
Pellegrini, C., Antonioli, L., Colucci, R., Blandizzi, C., & Fornai, M. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1856-5 · Cited by 270 · see citing works
Role of the gut-brain axis in energy and glucose metabolism
Wachsmuth, H. R., Weninger, S. N., & Duca, F. A. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00677-w · Cited by 269 · see citing works
Stilling, R. M., Ryan, F. J., Hoban, A. E., Shanahan, F., Clarke, G., Claesson, M. J., Dinan, T. G., & Cryan, J. F. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.07.009 · Cited by 233 · see citing works
Bosi, A., Banfi, D., Bistoletti, M., Giaroni, C., & Baj, A. (2020) · International Journal of Tryptophan Research · doi:10.1177/1178646920928984 · Cited by 221 · see citing works
Mind-altering with the gut: Modulation of the gut-brain axis with probiotics
Kim, N., Yun, M., Oh, Y. J., & Choi, H.-J. (2018) · Journal of Microbiology · doi:10.1007/s12275-018-8032-4 · Cited by 210 · see citing works
Microbe-host interactions: influence of the gut microbiota on the enteric nervous system
Hyland, N. P., & Cryan, J. F. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.06.027 · Cited by 207 · see citing works
Gut Microbiota: The Brain Peacekeeper
Mu, C., Yang, Y., & Zhu, W. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00345 · Cited by 188 · see citing works
McVey Neufeld, K. A., Perez‐Burgos, A., Mao, Y. K., Bienenstock, J., & Kunze, W. A. (2015) · Neurogastroenterology & Motility · doi:10.1111/nmo.12534 · Cited by 142 · see citing works
Self-citationYarandi, S. S., Kulkarni, S., Saha, M., Sylvia, K. E., Sears, C. L., & Pasricha, P. J. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.03.050 · Cited by 138 · see citing works
The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness
Hornig, M. (2013) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e32836208de · Cited by 138 · see citing works
The role of the microbiome in the neurobiology of social behaviour
Sarkar, A., Harty, S., Johnson, K. V. ‐., Moeller, A. H., Carmody, R. N., Lehto, S. M., Erdman, S. E., Dunbar, R. I. M., & Burnet, P. W. J. (2020) · Biological Reviews · doi:10.1111/brv.12603 · Cited by 135 · see citing works
KUWAHARA, A., MATSUDA, K., KUWAHARA, Y., ASANO, S., INUI, T., & MARUNAKA, Y. (2020) · Biomedical Research · doi:10.2220/biomedres.41.199 · Cited by 112 · see citing works
Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice
Stilling, R. M., Moloney, G. M., Ryan, F. J., Hoban, A. E., Bastiaanssen, T. F., Shanahan, F., Clarke, G., Claesson, M. J., Dinan, T. G., & Cryan, J. F. (2018) · eLife · doi:10.7554/elife.33070 · Cited by 106 · see citing works
Chandrasekharan, B., Saeedi, B. J., Alam, A., Houser, M., Srinivasan, S., Tansey, M., Jones, R., Nusrat, A., & Neish, A. S. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.03.045 · Cited by 94 · see citing works
Hung, L. Y., & Margolis, K. G. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00857-1 · Cited by 96 · see citing works
Gut microbiota regulates key modulators of social behavior
Parashar, A., & Udayabanu, M. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.11.002 · Cited by 88 · see citing works
Julio-Pieper, M., Bravo, J. A., Aliaga, E., & Gotteland, M. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12950 · Cited by 84 · see citing works
Beyond phylotyping: understanding the impact of gut microbiota on host biology
Reigstad, C. S., & Kashyap, P. C. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12134 · Cited by 66 · see citing works
What’s bugging your teen?—The microbiota and adolescent mental health
McVey Neufeld, K.-A., Luczynski, P., Seira Oriach, C., Dinan, T. G., & Cryan, J. F. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.005 · Cited by 56 · see citing works
Self-citationGut-to-Brain Axis in Autism Spectrum Disorders
Kraneveld, A. D., Szklany, K., de Theije, C. G. M., & Garssen, J. (2016) · International review of neurobiology · doi:10.1016/bs.irn.2016.09.001 · Cited by 47 · see citing works
- Authors
- McVey Neufeld, K. A., Mao, Y. K., Bienenstock, J., Foster, J. A., & Kunze, W. A.
- Affiliations
- St. Joseph’s Healthcare Hamilton (CA)
- Venue
- Neurogastroenterology & Motility
- Publisher
- Wiley
- Published
- 2012-11-27
- Volume
- 25
- Issue
- 2
- Pages
- 183
- ISSN
- 1350-1925 (ISSN-L)
- 1365-2982
- OpenAlex
- W1566099765
- Cited by
- 299
- References
- 8
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 19 · 2023: 16 · 2022: 29 · 2021: 36 · 2020: 26 · 2019: 23 · 2018: 27 · 2017: 19 · 2016: 33 · 2015: 15 · 2014: 10 · 2013: 14
- FWCI
- 12.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurogastroenterology & Motility (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institute for Physical Activity and Nutrition
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- gut microbiota, enteric nervous system, myenteric plexus, primary afferent neurons, neuronal excitability, germ-free mice, conventionalization, slow afterhyperpolarization, action potential, input resistance, gut-brain axis, jejunum
- MeSH terms
- Animals, Female, Germ-Free Life, Jejunum, Male, Membrane Potentials, Myenteric Plexus, Neurons, Afferent, Patch-Clamp Techniques, Mice, Metagenome
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