Activation in vagal afferents and central autonomic pathways: Early responses to intestinal infection with Campylobacter jejuni
Abstract
Abundant evidence now supports the idea that multiple pathways or mechanisms underlie communication from the immune system to the brain. The presence of a variety of mechanisms suggests that they may each contribute something different to immunosensory signaling. For instance, brain mediated immune signal transduction is dependent upon the presence of circulating mediators whereas peripheral sensory nerves are more likely to be important early on in an infection, prior to elevation of circulating cytokines, or in local infections within the terminal fields of these nerves. To test the hypothesis that local infection in the gut activates vagal sensory neurons, we assessed expression of the neuronal activation marker c-Fos in neurons in the vagal sensory ganglia and in the primary sensory relay nucleus for the vagus, the nucleus of the solitary tract (nTS) in mice treated orally either with saline or live Campylobacter jejuni (C. jejuni). Male CF1 mice were inoculated orally with either C. jejuni or saline, and c-Fos expression in the vagal sensory neurons and brain 4-12 h later was assessed via immunohistochemistry. Oral inoculation with C. jejuni led to a significant increase in c-Fos expression in neurons bilaterally in the vagal ganglia, in the absence of elevated levels of circulating pro-inflammatory cytokines. C. jejuni treatment activated neurons in the nTS, as well as in brain regions associated with primary viscerosensory pathways and the central autonomic network. These findings provide evidence that peripheral sensory neurons contribute an early signal to the brain regarding potential pathogens.
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Gut bacteria can interact with and activate the vagus nerve, thereby exerting effects upstream to the central nervous system.
“gut bacteria can interact with and activate the vagus nerve, thereby exerting effects upstream to the CNS.”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [58]
Changes in enteric neuron activity perceived by the vagus nerve are essential for mediating satiety, stress, and mood.
“Changes in enteric neuron activity perceived by the vagus nerve are essential for mediating satiety, stress, and mood (12, 58, 59).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [58]
Vagal sensory neuron activation via Campylobacter jejuni gut inoculation of mice resulted in direct activation of the neuronal activation marker c-Fos in the vagal sensory ganglia and the nucleus tractus solitarius (NTS) in the medulla oblongata.
“vagal sensory neuron activation via Campylobacter jejuni gut inoculation of mice resulted in direct activation of the neuronal activation marker c-Fos in the vagal sensory ganglia and the primary sensory relay nucleus for the vagus nerve, the nucleus tractus solitarius (NTS) in the medulla oblongata (Goehler et al., 2005).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Goehler et al., 2005
Gut bacteria utilize vagal afferents to alter hosts' emotional and behavioral responses, as evidenced by changes in c-Fos expression in vagal afferent cell bodies after oral Campylobacter jejuni.
“Evidence that gut bacteria utilize vagal afferents to alter their hosts' emotional and behavioral responses comes from studies observing changes in c-Fos expression in the cell bodies of vagal afferents following oral administration of Campylobacter jejuni (Goehler et al., 2005).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Goehler et al., 2005
Cites
Maier, S. F. (2003) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(03)00032-1 · Cited by 300 · see citing works
Lyte, M., Varcoe, J. J., & Bailey, M. T. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(98)00145-0 · Cited by 218 · see citing works
Self-citationWang, X. (2002) · World Journal of Gastroenterology · doi:10.3748/wjg.v8.i3.540 · Cited by 143 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J., & Cryan, J. F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102999108 · Cited by 3,888 · see citing works
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043 · see citing works
“by the vagus nerve are essential for mediating satiety, stress, and mood (12, 58, 59).”
BackgroundResultBercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.052 · Cited by 1,748 · see citing works
Dysbiosis of the gut microbiota in disease
Carding, S., Verbeke, K., Vipond, D. T., Corfe, B. M., & Owen, L. J. (2015) · Microbial Ecology in Health & Disease · doi:10.3402/mehd.v26.26191 · Cited by 1,710 · see citing works
The vagus nerve at the interface of the microbiota-gut-brain axis
Bonaz, B., Bazin, T., & Pellissier, S. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00049 · Cited by 1,397 · see citing works
Martin, C. R., Osadchiy, V., Kalani, A., & Mayer, E. A. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.04.003 · Cited by 1,284 · see citing works
Microbiota and neurodevelopmental windows: implications for brain disorders
Borre, Y. E., O’Keeffe, G. W., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.05.002 · Cited by 1,089 · see citing works
Control of brain development, function, and behavior by the microbiome
Sampson, T. R., & Mazmanian, S. K. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.011 · Cited by 1,093 · see citing works
Bercik, P., Park, A. J., Sinclair, D., Khoshdel, A., Lu, J., Huang, X., Deng, Y., Blennerhassett, P. A., Fahnestock, M., Moine, D., et al. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01796.x · Cited by 1,018 · see citing works
The Health Benefits of Dietary Fibre
Barber, T. M., Kabisch, S., Pfeiffer, A. F. H., & Weickert, M. O. (2020) · Nutrients · doi:10.3390/nu12103209 · Cited by 892 · see citing works
“The interactions within the gut microbiota–brain axis are likely to be complex and multi-directional [60,61] and implicate the release of by-products from gut microbes, including SCFAs, secondary bile acids and tryptophan metabolites [60,62].”
BackgroundBercik, P., Verdu, E. F., Foster, J. A., Macri, J., Potter, M., Huang, X., Malinowski, P., Jackson, W., Blennerhassett, P., Neufeld, K. A., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.06.063 · Cited by 674 · see citing works
Brain–Gut Interactions in Inflammatory Bowel Disease
Bonaz, B. L., & Bernstein, C. N. (2013) · Gastroenterology · doi:10.1053/j.gastro.2012.10.003 · Cited by 667 · see citing works
Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways
Maes, M., Berk, M., Goehler, L., Song, C., Anderson, G., Gałecki, P., & Leonard, B. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-66 · Cited by 629 · see citing works
Self-citationAit-Belgnaoui, A., Durand, H., Cartier, C., Chaumaz, G., Eutamene, H., Ferrier, L., Houdeau, E., Fioramonti, J., Bueno, L., & Theodorou, V. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.024 · Cited by 612 · see citing works
Gut Microbe to Brain Signaling: What Happens in Vagus…
Fülling, C., Dinan, T. G., & Cryan, J. F. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.008 · Cited by 590 · 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
The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications
Osadchiy, V., Martin, C. R., & Mayer, E. A. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.10.002 · Cited by 555 · see citing works
Browning, K. N., & Travagli, R. A. (2014) · Comprehensive Physiology · doi:10.1002/cphy.c130055 · Cited by 541 · see citing works
Microbiome–microglia connections via the gut–brain axis
Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180794 · Cited by 471 · see citing works
“Communication through the vagus nerve is essential for signals mediating satiety, stress, and mood, and these signals are governed by changes in enteric neuron activity and the behavior of gut microbes (Goehler et al., 2005; Forsythe et al., 2014; Browning et al., 2017).”
BackgroundAlcock, J., Maley, C. C., & Aktipis, C. A. (2014) · BioEssays · doi:10.1002/bies.201400071 · Cited by 454 · see citing works
Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health
Berding, K., Vlckova, K., Marx, W., Schellekens, H., Stanton, C., Clarke, G., Jacka, F., Dinan, T. G., & Cryan, J. F. (2021) · Advances in Nutrition · doi:10.1093/advances/nmaa181 · Cited by 451 · see citing works
Molecular and functional neuroscience in immunity
Pavlov, V. A., Chavan, S. S., & Tracey, K. J. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053158 · Cited by 444 · see citing works
Altered gut microbiota and activity in a murine model of autism spectrum disorders
de Theije, C. G. M., Wopereis, H., Ramadan, M., van Eijndthoven, T., Lambert, J., Knol, J., Garssen, J., Kraneveld, A. D., & Oozeer, R. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.12.005 · Cited by 433 · 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
Forsythe, P., Sudo, N., Dinan, T., Taylor, V. H., & Bienenstock, J. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.05.058 · Cited by 429 · see citing works
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
Microbes 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
Gut microbial molecules in behavioural and neurodegenerative conditions
Needham, B. D., Kaddurah-Daouk, R., & Mazmanian, S. K. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-00381-0 · Cited by 379 · see citing works
The vagus nerve in appetite regulation, mood, and intestinal inflammation
Browning, K. N., Verheijden, S., & Boeckxstaens, G. E. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.10.046 · Cited by 361 · see citing works
Probiotics and the microbiota-gut-brain axis: Focus on psychiatry
Mörkl, S., Butler, M. I., Holl, A., Cryan, J. F., & Dinan, T. G. (2020) · Current Nutrition Reports · doi:10.1007/s13668-020-00313-5 · Cited by 337 · see citing works
LYTE, M., LI, W., OPITZ, N., GAYKEMA, R., & GOEHLER, L. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.06.019 · Cited by 334 · see citing works
Self-citationThe neuroendocrinology of the microbiota-gut-brain axis: a behavioural perspective
Cussotto, S., Sandhu, K. V., Dinan, T. G., & Cryan, J. F. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.04.002 · Cited by 326 · see citing works
“The vagus nerve has received much attention as a conduit of signals from the gut to the brain and vice versa (Goehler et al., 2000; Goehler et al., 1999; Goehler et al., 2005).”
BackgroundEffects 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
Microbiota-gut-brain axis and the central nervous system
Zhu, X., Han, Y., Du, J., Liu, R., Jin, K., & Yi, W. (2017) · Oncotarget · doi:10.18632/oncotarget.17754 · Cited by 308 · see citing works
Modulation of Gut Microbiota–Brain Axis by Probiotics, Prebiotics, and Diet
Liu, X., Cao, S., & Zhang, X. (2015) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5b02404 · Cited by 304 · see citing works
Harshaw, C. (2015) · Psychological Bulletin · doi:10.1037/a0038101 · Cited by 302 · see citing works
Goehler, L. E., Park, S. M., Opitz, N., Lyte, M., & Gaykema, R. P. A. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.08.009 · Cited by 287 · see citing works
Self-citationToll-like Receptors 3, 4, and 7 Are Expressed in the Enteric Nervous System and Dorsal Root Ganglia
Barajon, I., Serrao, G., Arnaboldi, F., Opizzi, E., Ripamonti, G., Balsari, A., & Rumio, C. (2009) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.2009.953539 · Cited by 287 · see citing works
Stress at the intestinal surface: catecholamines and mucosa–bacteria interactions
Lyte, M., Vulchanova, L., & Brown, D. R. (2011) · Cell and Tissue Research · doi:10.1007/s00441-010-1050-0 · Cited by 281 · see citing works
Self-citationThe vagal innervation of the gut and immune homeostasis
Matteoli, G., & Boeckxstaens, G. E. (2013) · Gut · doi:10.1136/gutjnl-2012-302550 · Cited by 276 · see citing works
Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases
Spielman, L. J., Gibson, D. L., & Klegeris, A. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.08.005 · Cited by 266 · see citing works
Han, Y., Wang, B., Gao, H., He, C., Hua, R., Liang, C., Zhang, S., Wang, Y., Xin, S., & Xu, J. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s384949 · Cited by 265 · see citing works
Li, W., Dowd, S. E., Scurlock, B., Acosta-Martinez, V., & Lyte, M. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.12.004 · Cited by 246 · see citing works
Self-citationPerez-Burgos, A., Wang, B., Mao, Y.-K., Mistry, B., Neufeld, K.-A. M., Bienenstock, J., & Kunze, W. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00128.2012 · Cited by 235 · see citing works
Microbiome disturbances and autism spectrum disorders
Rosenfeld, C. S. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.063826 · Cited by 229 · see citing works
On communication between gut microbes and the brain
Forsythe, P., Kunze, W. A., & Bienenstock, J. (2012) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e3283572ffa · Cited by 137 · see citing works
Microbial endocrinology: Host-bacteria communication within the gut microbiome
Sandrini, S., Aldriwesh, M., Alruways, M., & Freestone, P. (2015) · Journal of Endocrinology · doi:10.1530/joe-14-0615 · Cited by 130 · see citing works
Gut microbes in neurocognitive and mental health disorders
Halverson, T., & Alagiakrishnan, K. (2020) · Annals of Medicine · doi:10.1080/07853890.2020.1808239 · Cited by 125 · see citing works
Goehler, L. E., Lyte, M., & Gaykema, R. P. A. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.02.005 · Cited by 127 · see citing works
Self-citationLefter, R., Ciobica, A., Timofte, D., Stanciu, C., & Trifan, A. (2019) · Medicina · doi:10.3390/medicina56010011 · Cited by 120 · see citing works
A neuro-immune model of myalgic encephalomyelitis/chronic fatigue syndrome
Morris, G., & Maes, M. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-012-9324-8 · Cited by 117 · see citing works
The microbiota–gut–brain axis: learning from intestinal bacteria?
Bercik, P. (2011) · Gut · doi:10.1136/gut.2010.226779 · Cited by 87 · see citing works
Bested, A. C., Logan, A. C., & Selhub, E. M. (2013) · Gut Pathogens · doi:10.1186/1757-4749-5-4 · Cited by 84 · see citing works
Gut–Brain Axis in Regulation of Blood Pressure
Yang, T., & Zubcevic, J. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00845 · Cited by 74 · see citing works
Lyte, M., Chapel, A., Lyte, J. M., Ai, Y., Proctor, A., Jane, J.-L., & Phillips, G. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146406 · Cited by 62 · see citing works
Self-citationThe microbiome and gut endocannabinoid system in the regulation of stress responses and metabolism
Srivastava, R. K., Lutz, B., & Ruiz de Azua, I. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.867267 · Cited by 56 · see citing works
Gut-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
Sashihara, T., Nagata, M., Mori, T., Ikegami, S., Gotoh, M., Okubo, K., Uchida, M., & Itoh, H. (2013) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2012-0490 · Cited by 46 · see citing works
The Many Faces of Microbiota-Gut-Brain Axis in Autism Spectrum Disorder
Gonçalves, C. L., Doifode, T., Rezende, V. L., Costa, M. A., Rhoads, J. M., & Soutullo, C. A. (2024) · Life Sciences · doi:10.1016/j.lfs.2023.122357 · Cited by 42 · see citing works
Xiong, Q., Tang, F., Li, Y., Xie, F., Yuan, L., Yao, C., Wu, R., Wang, J., Wang, Q., & Feng, P. (2022) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2022.110983 · Cited by 33 · see citing works
Oduro-Donkor, D., Turner, M. C., Farnaud, S., Renshaw, D., Kyrou, I., Hanson, P., Hattersley, J., Weickert, M. O., Menon, V., Randeva, H. S., et al. (2020) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2020.1801412 · Cited by 33 · see citing works
Clostridioides difficile and neurological disorders: new perspectives
Biazzo, M., Allegra, M., & Deidda, G. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.946601 · Cited by 11 · see citing works
Homeostatic and Circadian Control of Food Intake: Clinical Strategies to Prevent Overconsumption
Drapeau, V., & Gallant, A. R. (2013) · Current Obesity Reports · doi:10.1007/s13679-012-0038-3 · Cited by 10 · see citing works
- Authors
- Goehler, L. E., Gaykema, R. P. A., Opitz, N., Reddaway, R., Badr, N., & Lyte, M.
- Affiliations
- University of Virginia (US)
- Hennepin County Medical Center (US)
- Minnesota State University, Mankato (US)
- Corresponding author
- Goehler, Lisa E.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 19
- Issue
- 4
- Pages
- 334-344
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W1969140399
- Cited by
- 442
- References
- 3
- Citations by year
- 2026: 15 · 2025: 35 · 2024: 38 · 2023: 40 · 2022: 39 · 2021: 30 · 2020: 45 · 2019: 19 · 2018: 30 · 2017: 17 · 2016: 20 · 2015: 15 · 2014: 17 · 2013: 18 · 2012: 13
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r21mh064648-02)
- National Institute of Mental Health (MH-50431, MH64648, R01MH050431)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- Campylobacter jejuni, vagal afferents, vagal afferent neurons, c-fos, nucleus tractus solitarius, central autonomic network, gut-brain signaling, intestinal infection, vagal ganglia, peripheral sensory neurons
- MeSH terms
- Animals, Brain, Campylobacter Infections, Cecum, Ganglia, Autonomic, Male, Vagus Nerve, Neuroimmunomodulation, Campylobacter jejuni, Cytokines, Proto-Oncogene Proteins c-fos, Enteric Nervous System, Visceral Afferents, Mice
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