Gut Microbiota as a Systemic Regulator: Immunological and Neurological Implications Beyond Digestive Disease
DOI:
https://doi.org/10.64784/218Keywords:
Gut microbiota, Gut-brain axis, Dysbiosis, Systemic inflammation, Neuroinflammation, Immune regulation, Autoimmune disease, Metabolic disease, Cardiovascular disease, Neurodegenerative disease, Microbiome, Chronic inflammation, Intestinal permeability, Probiotics, Fecal microbiota transplantationAbstract
The gut microbiota has emerged as a fundamental regulator of systemic human physiology, extending its influence far beyond the gastrointestinal tract. Recent advances in microbiome research have demonstrated that intestinal microorganisms participate actively in metabolic regulation, immune homeostasis, neuroimmune communication, inflammatory signaling, and chronic disease progression. The present review aimed to analyze current scientific evidence regarding the relationship between gut microbiota and systemic diseases, with special emphasis on immunological and neurological implications beyond digestive pathology. A structured narrative review methodology based on the Scientific Method was employed through analysis of peer-reviewed literature indexed in internationally recognized scientific databases including PubMed, Scopus, ScienceDirect, and SpringerLink. The review integrated multidisciplinary evidence involving gastroenterology, neurology, immunology, microbiology, metabolism, and translational medicine. The selected studies evaluated mechanisms associated with intestinal dysbiosis, systemic inflammation, gut–brain axis signaling, immune dysregulation, microbial metabolites, and microbiota-targeted therapeutic strategies. The analyzed evidence demonstrated that alterations in gut microbial diversity are strongly associated with chronic inflammatory diseases, obesity, type 2 diabetes mellitus, cardiovascular disease, autoimmune disorders, neurodegenerative pathology, and psychiatric conditions. Key mechanisms identified included increased intestinal permeability, chronic low-grade inflammation, abnormal immune activation, altered short-chain fatty acid production, and neuroimmune dysregulation mediated through the gut–brain axis. Furthermore, microbiota-targeted interventions such as probiotics, prebiotics, dietary modulation, postbiotics, and fecal microbiota transplantation demonstrated promising therapeutic potential in restoring microbial balance and reducing inflammatory activity.
References
1. Y. Fan and O. Pedersen, “Gut microbiota in human metabolic health and disease,” Nature Reviews Microbiology, vol. 19, no. 1, pp. 55–71, 2021, doi: 10.1038/s41579-020-0433-9.
2. S. V. Lynch and O. Pedersen, “The human intestinal microbiome in health and disease,” New England Journal of Medicine, vol. 375, no. 24, pp. 2369–2379, 2016, doi: 10.1056/NEJMra1600266.
3. J. F. Cryan et al., “The microbiota-gut-brain axis,” Physiological Reviews, vol. 99, no. 4, pp. 1877–2013, 2019, doi: 10.1152/physrev.00018.2018.
4. J. S. Loh et al., “Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases,” Signal Transduction and Targeted Therapy, vol. 9, article 37, 2024, doi: 10.1038/s41392-024-01743-1.
5. Z. Ma et al., “A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation,” Signal Transduction and Targeted Therapy, vol. 9, article 237, 2024, doi: 10.1038/s41392-024-01946-6.
6. S. P. Wiertsema, J. van Bergenhenegouwen, J. Garssen, and L. M. J. Knippels, “The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies,” Nutrients, vol. 13, no. 3, article 886, 2021, doi: 10.3390/nu13030886.
7. Y. Belkaid and T. W. Hand, “Role of the microbiota in immunity and inflammation,” Cell, vol. 157, no. 1, pp. 121–141, 2014, doi: 10.1016/j.cell.2014.03.011.
8. N. Kamada, S. U. Seo, G. Y. Chen, and G. Núñez, “Role of the gut microbiota in immunity and inflammatory disease,” Nature Reviews Immunology, vol. 13, no. 5, pp. 321–335, 2013, doi: 10.1038/nri3430.
9. W. Yang and Y. Cong, “Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases,” Cellular & Molecular Immunology, vol. 18, pp. 866–877, 2021, doi: 10.1038/s41423-021-00661-4.
10. F. Di Vincenzo et al., “Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review,” International Journal of Molecular Sciences, vol. 25, no. 4, article 2297, 2024.
11. J. Correale, M. Farez, and M. Gaitán, “The role of the gut microbiota in multiple sclerosis,” Nature Reviews Neurology, vol. 18, pp. 544–558, 2022.
12. A. Rutsch, J. B. Kantsjö, and F. Ronchi, “The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology,” Frontiers in Immunology, vol. 11, article 604179, 2020, doi: 10.3389/fimmu.2020.604179.
13. H. Ullah et al., “The gut microbiota–brain axis in neurological disorder,” Frontiers in Neuroscience, vol. 17, article 1225875, 2023, doi: 10.3389/fnins.2023.1225875.
14. C. L. Hsu and B. Schnabl, “The gut–liver axis and gut microbiota in health and liver disease,” Nature Reviews Microbiology, vol. 21, pp. 719–733, 2023.
15. F. C. Ross et al., “The interplay between diet and the gut microbiome: implications for health and disease,” Nature Reviews Microbiology, vol. 22, pp. 671–686, 2024, doi: 10.1038/s41579-024-01068-4.
16. T. P. M. Scheithauer et al., “Gut microbiota as a trigger for metabolic inflammation in obesity and type 2 diabetes,” Frontiers in Immunology, vol. 11, article 571731, 2020.
17. R. Sanchez-Gimenez et al., “Gut microbiota-derived metabolites and cardiovascular disease risk: a systematic review of prospective cohort studies,” Nutrients, vol. 14, no. 13, article 2654, 2022.
18. W. H. W. Tang, T. Kitai, and S. L. Hazen, “Gut microbiota in cardiovascular health and disease,” Circulation Research, vol. 120, no. 7, pp. 1183–1196, 2017, doi: 10.1161/CIRCRESAHA.117.309715.
19. A. F. Peery et al., “AGA clinical practice guideline on fecal microbiota-based therapies for select gastrointestinal diseases,” Gastroenterology, vol. 166, no. 3, pp. 409–434, 2024.
20. B. H. Mullish et al., “The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: joint British Society of Gastroenterology and Healthcare Infection Society guidelines,” Gut, vol. 73, no. 3, pp. 409–434, 2024.
