Neuroimmune Mechanisms in Gastrointestinal Disorders: Integrating Gut–Brain Axis Signaling into Clinical and Diagnostic Frameworks

Authors

DOI:

https://doi.org/10.64784/128

Keywords:

Neuroimmune interactions, gut–brain axis, gastrointestinal diseases, inflammatory bowel disease, irritable bowel syndrome, microbiota, visceral hypersensitivity, vagus nerve, neurogastroenterology, immune modulation

Abstract

Neuroimmune interactions have emerged as a central framework for understanding the complexity of gastrointestinal diseases, integrating immune regulation, neural signaling, and microbiota-driven mechanisms within the gut–brain axis. This review synthesizes current evidence on the role of neuroimmune pathways in both inflammatory and functional gastrointestinal disorders, with particular emphasis on inflammatory bowel disease and irritable bowel syndrome. The analyzed literature demonstrates that gastrointestinal symptom generation and disease expression result from dynamic interactions among immune cells, enteric and autonomic neural circuits, microbial signaling, and stress-related modulation rather than from isolated pathological processes. In inflammatory conditions, immune dysregulation and macrophage-mediated pathways predominate, while neural and autonomic mechanisms contribute to symptom persistence and variability. In functional disorders, immune–neural coupling, mast cell–nerve interactions, and visceral sensory sensitization emerge as key drivers of pain and altered bowel habits despite minimal structural abnormalities. Across both disease categories, the intestinal microbiota acts as a cross-cutting regulator influencing immune tone, barrier integrity, and neural responsiveness. From a clinical and diagnostic perspective, these findings support a mechanism-based approach that complements traditional inflammatory and structural assessments with neuroimmune-informed reasoning. This integrative framework has particular relevance for medical education and clinical practice in diverse healthcare settings, including Latin America, where resource variability necessitates strong pathophysiological interpretation. Overall, neuroimmune models provide a coherent and biologically grounded perspective for advancing diagnosis, teaching, and future translational strategies in gastroenterology.

References

[1] G. Mayer, K. Tillisch, and E. A. Gupta, “Gut/brain axis and the microbiota,” Journal of Clinical Investigation, vol. 125, no. 3, pp. 926–938, 2015, doi: 10.1172/JCI76304.

[2] J. F. Cryan and T. G. Dinan, “Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour,” Nature Reviews Neuroscience, vol. 13, no. 10, pp. 701–712, 2012, doi: 10.1038/nrn3346.

[3] M. E. Gershon and J. Tack, “The serotonin signaling system: From basic understanding to drug development for functional GI disorders,” Gastroenterology, vol. 132, no. 1, pp. 397–414, 2007, doi: 10.1053/j.gastro.2006.11.002.

[4] D. J. Powell, M. E. Gershon, J. F. Holzer, and M. A. Sharkey, “Neuroimmune interactions in inflammatory bowel disease,” Gastroenterology, vol. 143, no. 6, pp. 1534–1544, 2012, doi: 10.1053/j.gastro.2012.09.038.

[5] S. C. Powley, A. Phillips, and L. A. Bercik, “Vagal pathways and immune regulation in gastrointestinal disease,” Autonomic Neuroscience, vol. 182, pp. 1–7, 2014, doi: 10.1016/j.autneu.2013.12.006.

[6] M. Bonaz, V. Sinniger, and S. Pellissier, “The vagus nerve in the neuro-immune axis: Implications in gastrointestinal diseases,” Nature Reviews Gastroenterology & Hepatology, vol. 14, no. 1, pp. 36–45, 2017, doi: 10.1038/nrgastro.2016.160.

[7] S. Pellissier, V. Sinniger, and M. Bonaz, “The intestinal microbiota and the vagus nerve,” Neurogastroenterology & Motility, vol. 26, no. 9, pp. 1299–1310, 2014, doi: 10.1111/nmo.12371.

[8] R. J. Xavier and D. K. Podolsky, “Unravelling the pathogenesis of inflammatory bowel disease,” Nature, vol. 448, no. 7152, pp. 427–434, 2007, doi: 10.1038/nature06005.

[9] J. R. McKay and L. M. P. Green, “The immune system and irritable bowel syndrome,” Nature Reviews Gastroenterology & Hepatology, vol. 14, no. 9, pp. 521–532, 2017, doi: 10.1038/nrgastro.2017.89.

[10] S. G. Vanner, E. Macnaughton, and G. L. Grundy, “Sensory neuron–immune interactions in the gut,” Nature Reviews Gastroenterology & Hepatology, vol. 9, no. 3, pp. 143–152, 2012, doi: 10.1038/nrgastro.2011.252.

[11] A. L. Buhner and P. R. Camilleri, “Visceral hypersensitivity in functional gastrointestinal disorders,” Gut, vol. 63, no. 5, pp. 789–797, 2014, doi: 10.1136/gutjnl-2013-305695.

[12] M. G. Keightley, Q. Wang, and S. R. Wallace, “Enteric glia and immune regulation in the gut,” American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 313, no. 2, pp. G118–G130, 2017, doi: 10.1152/ajpgi.00064.2017.

[13] S. De Schepper, S. Verheijden, J. Aguilera-Lizarraga, J. V. Viola, and G. Boeckxstaens, “Self-maintaining gut macrophages and their role in intestinal homeostasis,” Nature Reviews Gastroenterology & Hepatology, vol. 15, no. 9, pp. 555–566, 2018, doi: 10.1038/s41575-018-0027-7.

[14] G. Barbara, M. Grover, E. Bercik, R. J. Corsetti, and M. Mayer, “Rome Foundation Working Team Report on immune activation in IBS,” Gastroenterology, vol. 156, no. 4, pp. 913–933, 2019, doi: 10.1053/j.gastro.2018.11.060.

[15] M. Spiller and Q. Aziz, “Neuroimmune mechanisms in IBS,” Gut, vol. 63, no. 6, pp. 1043–1055, 2014, doi: 10.1136/gutjnl-2013-305216.

[16] E. A. Grubišić and G. Boeckxstaens, “The role of mast cells in gastrointestinal disorders,” Gut, vol. 65, no. 9, pp. 1556–1564, 2016, doi: 10.1136/gutjnl-2015-309291.

[17] M. Vanuytsel, J. Tack, and G. E. Boeckxstaens, “Treatment of functional gastrointestinal disorders targeting the gut–brain axis,” Nature Reviews Gastroenterology & Hepatology, vol. 11, no. 10, pp. 675–685, 2014, doi: 10.1038/nrgastro.2014.123.

[18] R. D. Moloney, T. G. Dinan, and J. F. Cryan, “Stress, the gut–brain axis and immune modulation,” Neurobiology of Stress, vol. 4, pp. 49–60, 2016, doi: 10.1016/j.ynstr.2016.02.002.

[19] G. E. Boeckxstaens, M. Camilleri, J. Sifrim, J. Houghton, and J. Tack, “Fundamentals of neurogastroenterology,” Gastroenterology, vol. 154, no. 6, pp. 1396–1407, 2018, doi: 10.1053/j.gastro.2018.02.003.

[20] M. Bonaz, S. Pellissier, V. Sinniger, and M. Clarençon, “Vagus nerve stimulation: A new promising therapeutic tool in inflammatory bowel disease,” Journal of Internal Medicine, vol. 282, no. 1, pp. 46–63, 2017, doi: 10.1111/joim.12611

Downloads

Published

2026-01-31

How to Cite

[1]
César Augusto Rojas Landa, Trans., “Neuroimmune Mechanisms in Gastrointestinal Disorders: Integrating Gut–Brain Axis Signaling into Clinical and Diagnostic Frameworks”, TheSci, vol. 3, no. 1, Jan. 2026, doi: 10.64784/128.