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Evidences for vagus nerve in maintenance of immune balance and transmission of immune information from gut to brain in STM-infected rats
Open accessAbstract
AIM: To determine whether Salmonella Typhimurium (STM)in gastrointestinal tract can induce the functional activation of brain, whether the vagus nerve involves in signaling immune information from gastrointestinal tract to brain and how it influences the immune function under natural infection condition. METHODS: Animal model of gastrointestinal tract infection in the rat was established by an intubation of Salmonella Typhimurium (STM) into stomach to mimic the condition of natural bacteria infection. Subdiagphragmatic vagotomy was performed in some of the animals 28 days before infection. The changes of Fos expression visualized with immunohistochemistry technique in hypothalamic paraventricular nucleus (PVN) and superaoptic nucleus (SON) were counted. Meanwhile, the percentage and the Mean Intensities of Fluorescent (MIFs) of CD4+ and CD8+ T cells in peripheral blood were measured by using flow cytometry (FCM), and the pathological changes in ileum and mesenteric lymph node were observed in HE stained sections. RESULTS: In bacteria-stimulated groups, inflammatory pathological changes were seen in ileum and mesenteric lymph node. The percentages of CD4+ T cells in peripheral blood were decreased from 42%+/-4.5% to 34%+/-4.9% (P<0.05) and MIFs of CD8+ T cells were also decreased from 2.9+/-0.39 to 2.1+/-0.36 (P<0.05) with STM stimulation. All of them proved that our STM-infection model was reliable. Fos immunoreactive (Fos-ir) cells in PVN and SON increased significantly with STM stimulation, from 189+/-41 to 467+/-62 (P<0.05) and from 64+/-21 to 282+/-47 (P<0.05) individually, which suggested that STM in gastrointestinal tract induced the functional activation of brain. Subdiagphragmatic vagotomy attenuated Fos expression in PVN and SON induced by STM, from 467+/-62 to 226+/-45 (P<0.05) and from 282+/-47 to 71+/-19 (P<0.05) individually, and restored the decreased percentages of CD4+ T cells induced by STM from 34%+/-4.9% to original level 44%+/-6.0% (P<0.05). In addition, subdiagphragmatic vagotomy itself also decreased the percentages of CD8+ T cells (from 28%+/-3.0% to 21%+/-5.9%, P<0.05) and MIFs of CD4+ (from 6.6+/-0.6 to 4.9+/-1.0, P<0.05) and CD8+ T cells (from 2.9+/-0.39 to 1.4+/-0.34, P<0.05). Both of them manifested the important role of vagus nerve in transmitting immune information from gut to brain and maintaining the immune balance of the organism. CONCLUSION: Vagus nerve does involve in transmitting abdominal immune information into the brain in STM infection condition and play an important role in maintenance of the immune balance of the organism.
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“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 [32]
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“and that neuronal activity in the PVN induced by bacterial colonization is blocked by subdiaphragmatic vagotomy (Wang et al., 2002).”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as Wang et al., 2002
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Vagal sensory pathway for the gut-brain communication
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Wang, X., Wang, B., Zhang, X., Duan, X., Guo, X., & Ju, G. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000035801.81825.2a · Cited by 33
“Fos-immunoreactive (ir) cells in brain were visualized by using avidin–biotin–peroxidase immunohistochemical technique as described previously (20).”
MethodLiving Therapeutics: The Next Frontier of Precision Medicine
Kelly, V. W., Liang, B. K., & Sirk, S. J. (2020) · ACS Synthetic Biology · doi:10.1021/acssynbio.0c00444 · Cited by 30
“(47)Wang, X., et al. (2002) Evidences for vagus nerve in maintenance”
BackgroundHan, F. (2003) · World Journal of Gastroenterology · doi:10.3748/wjg.v9.i5.1045 · Cited by 31
Riley, T. P., Neal‐McKinney, J. M., Buelow, D. R., Konkel, M. E., & Simasko, S. M. (2013) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2013.01.009 · Cited by 31
“Previously Wang and co-workers (Wang et al., 2002) found that a physical vagotomy partially prevented the induction of c-Fos-ir in hypothalamic nuclei by oral inoculation with S. typhimurium.”
InfluentialHang, C., Shi, J., Li, J., Wu, W., Li, W., & Yin, H.-X. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i6.875 · Cited by 31
Acupuncture influences multiple diseases by regulating gut microbiota
Xu, H., Luo, Y., Li, Q., & Zhu, H. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1371543 · Cited by 33
Melamed, E., Palmer, J. L., & Fonken, C. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1019877 · Cited by 26
Tu, X., Li, S., Zhao, L., Xiao, R., Wang, X., & Zhu, F. (2017) · Virologica Sinica · doi:10.1007/s12250-017-3984-9 · Cited by 28
“Immune information is also transmitted to the brain through rapid neural pathways that activate primary afferent nerve fibers in response to peripheral cytokine release (Dantzer et al., 2000; Wang et al., 2002).”
BackgroundLyte, J. M., Keane, J., Eckenberger, J., Anthony, N. B., Shrestha, S., Marasini, D., Daniels, K. M., Caputi, V., Donoghue, A. M., & Lyte, M. (2021) · Microbiome · doi:10.1186/s40168-020-00962-2 · Cited by 26
“While the cecum is therefore of particular relevance in mechanisms of neurochemical-mediated avian host-pathogen interaction, in rodents, bacterial colonization and infection of the cecum have been demonstrated to rapidly affect brainstem function and host behavior, underscoring the relevance of the cecal microbiome o…”
BackgroundMravec, B., Gidron, Y., Kukanova, B., Bízik, J., Kiss, A., & Hulín, I. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.07.003 · Cited by 26
Stress and the Gut-Brain Axis: Implications for Cancer, Inflammation and Sepsis
Moughnyeh, M., Brawner, K. M., Kennedy, B. A., Yeramilli, V. A., Udayakumar, N., Graham, J. A., & Martin, C. A. (2021) · Journal of Surgical Research · doi:10.1016/j.jss.2021.02.055 · Cited by 24
Prescott, S. L., Logan, A. C., D’Adamo, C. R., Holton, K. F., Lowry, C. A., Marks, J., Moodie, R., & Poland, B. D. (2024) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph21020120 · Cited by 27
“…behavior in animals [199]; C. jejuni is a microbe that causes gastritis in humans, but the amounts administered were far below a pathogenic level, and the mechanism of this gut microbe-induced brain activity was determined to be direct gut-to-brain communication via the vagus nerve [200–202].”
BackgroundSymbiosis—Evolution’s Co-Author
Zook, D. P. (2015) · Interdisciplinary evolution research · doi:10.1007/978-3-319-16345-1_2 · Cited by 25
“Intriguing and profound linkages usually involving complex chemical signaling of the gut to the brain and vice versa are being consistently reported (Wang 2002; Forsythe et al. 2010).”
BackgroundLv, K., Fan, Y., Xu, L., & Xu, M. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i20.3607 · Cited by 22
Bendriss, G., MacDonald, R. S., & McVeigh, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241511978 · Cited by 25
Ultrastructure of junction areas between neurons and astrocytes in rat supraoptic nuclei
Duan, L., Yuan, H. M., Su, C., Liu, Y., & Rao, Z. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i1.117 · Cited by 18
“The osmotic, immune, and noxious information from these peripheral receptors could transmit to medullary nuclei (medullary visceral zone-MVZ that include nucleus of the tractus solitarius and ventrolateral medulla) via vagal nerve[ 4-8 ].”
BackgroundCampolim, C. M., Schimenes, B. C., Veras, M. M., Kim, Y., & Prada, P. O. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1401800 · Cited by 20
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Zhou, L., Lin, X., Ma, X., Liu, Y., Ma, L., Chen, Z., Chen, H., Si, L., & Chen, X. (2020) · International Journal of Neuroscience · doi:10.1080/00207454.2019.1706504 · Cited by 16
“In this study, vagotomy causes an ACh deficiency and inhibits T cells proliferation and differentiation [38,39], which makes the mice fail to respond to MOG35–55 as usual and finally manifests an amelioration effect in EAE.”
BackgroundKaur, A., Chopra, K., Kaur, I. P., & Rishi, P. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01568 · Cited by 18
Lyte, M. (2009) · Surgery · doi:10.1016/j.surg.2009.06.002 · Cited by 16
Parois, S. P., Duttlinger, A. W., Richert, B. T., Lindemann, S. R., Johnson, J. S., & Marchant, J. N. (2020) · Frontiers in Veterinary Science · doi:10.3389/fvets.2020.00140 · Cited by 16
Parois, S. P., Eicher, S. D., Lindemann, S. R., & Marchant, J. N. (2021) · Scientific Reports · doi:10.1038/s41598-021-03565-5 · Cited by 17
Crime and Nourishment: A Narrative Review Examining Ultra-Processed Foods, Brain, and Behavior
Prescott, S. L., Logan, A. C., LaFata, E. M., Naik, A., Nelson, D. H., Robinson, M. B., & Soble, L. (2024) · Dietetics · doi:10.3390/dietetics3030025 · Cited by 19
Significance of vagus nerve function in terms of pathogenesis of psychosocial disorders
Kakinuma, Y. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104934 · Cited by 15
Multiple sclerosis and the microbiota
Engelenburg, H. J., Lucassen, P. J., Sarafian, J. T., Parker, W., & Laman, J. D. (2022) · Evolution Medicine and Public Health · doi:10.1093/emph/eoac009 · Cited by 13
“This route of communication is observed, for example, when infection of the gastrointestinal system with specific bacteria transmits abdominal immune information to the brain via that nerve [29].”
BackgroundZhang, L., Zhang, Y., Jiang, X., Mao, L., Xia, Y., Fan, Y., Li, N., Jiang, Z., Qin, X., Jiang, Y., et al. (2022) · Toxicology · doi:10.1016/j.tox.2022.153390 · Cited by 13
The Role of the Microbiome in the Relationship of Asthma and Affective Disorders
Trueba, A. F., Ritz, T., & Trueba, G. A. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-20215-0_13 · Cited by 13
Banerjee, A., Pradhan, L. K., Sahoo, P. K., Jena, K. K., Chauhan, N. R., Chauhan, S., & Das, S. K. (2021) · Archives of Microbiology · doi:10.1007/s00203-021-02276-9 · Cited by 13
Cytokines in Neural Signaling to the Brain
Goehler, L. (2008) · Neuroimmune biology · doi:10.1016/s1567-7443(07)10016-8 · Cited by 12
Effects of common plastic products heat exposure on cognition: Mediated by gut microbiota
Hu, N., Pan, D., Yang, Y. H., Pu, L., He, X., Wang, H., Zhang, X., Du, Y., Yu, Z., He, S., et al. (2023) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2023.114758 · Cited by 12
Gut microbiota in Parkinson’s disease patients: hospital-based study
Khedr, E. M., Ali, A. M., Daef, E., Hassan, H. M., Alaa, A., & Gamea, A. (2021) · The Egyptian Journal of Neurology Psychiatry and Neurosurgery · doi:10.1186/s41983-021-00407-z · Cited by 11
“Others found that Bacteroides abundance correlated with motor symptom severity as defined by UPDRS part III motor scores [38] and in another study, the abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty [39].”
BackgroundModulation of amoebic hepatic abscess by the parasympathetic system
Muñoz‐Ortega, M. H., Quintanar‐Stephano, A., Lorenzana, M. G., CAMPOS‐ESPARZA, M. R., Silva-Briano, M., Adabache-Ortíz, A., Campos-Rodrı́guez, R., Rodríguez, M. G., & Ventura‐Juárez, J. (2010) · Parasite Immunology · doi:10.1111/j.1365-3024.2010.01245.x · Cited by 10
Gut microbiota analysis and its significance in vasovagal syncope in children
Bai, W., Chen, S. Y., Tang, C., Qi, J., Cui, Q., Xu, M., Du, J., & Jin, H. (2019) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000086 · Cited by 10
Xie, Z.-F., Wang, S., Gao, Y., Zhang, Y.-D., Han, Y., Huang, J., Gao, M.-N., & Wang, C.-G. (2024) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-024-05091-0 · Cited by 9
“Specifically, enter-oendocrine cells can sense various signals from chemical stimuli, microbiota, and metabolites to regulate the release of serotonin and different gut hormones [104–108].”
Miranda, V., Laarej, K., & Cavaliere, C. (2026) · Cells · doi:10.3390/cells15010082 · Cited by 10
“The structure of the microbiota strongly affects CNS activity: rats dosed with Bifidobacterium infantis for two weeks showed increased levels of tryptophan in the blood, emphasising the communication between certain microorganisms in the gut and the CNS [158].”
Gut microbiota sPARk vagus nerve excitation
Singh, A., Serre, C. B. D. L., & de Lartigue, G. (2020) · The Journal of Physiology · doi:10.1113/jp279763 · Cited by 9
Microbiome: The Missing Link in Neuropsychiatric Disorders
Evrensel, A., & Ceylan, M. E. (2017) · EMJ Innovation · doi:10.33590/emjinnov/10313424 · Cited by 9
Metadata
- Authors
- Wang, X.
- Affiliations
- Air Force Medical University (CN)
- Corresponding author
- Wang, Xi
- ORCID
- Wang, Xi
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2002
- Volume
- 8
- Issue
- 3
- Pages
- 540
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC4656439
- OpenAlex
- W155664710
- Cited by
- 143
- References
- 50
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 6 · 2022: 6 · 2021: 18 · 2020: 14 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 9 · 2015: 11 · 2014: 6 · 2013: 3 · 2012: 4
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Gastroenterology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- vagus nerve, gut-brain axis, Salmonella typhimurium, gastrointestinal infections, vagotomy, Fos expression, paraventricular nucleus, supraoptic nucleus, CD4+ T cells, CD8+ T cells, immune homeostasis, intestinal inflammation, mesenteric lymph nodes, rats
- MeSH terms
- Animals, Gastrointestinal Diseases, Male, Salmonella Infections, Animal, Salmonella typhimurium, Vagus Nerve, Neuroimmunomodulation, Rats, Sprague-Dawley, Rats
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