The Gut-Brain Axis and Mental Health: A Comprehensive Review of Microbiome Based Therapeutic Approaches

Background: Emerging evidence implicates the gut-brain axis (GBA) as a critical bidirectional communication network influencing neurological and psychiatric health. The gut microbiome, comprising trillions of microorganisms, produces neurotransmitters, neuroactive metabolites, and immune mediators that modulate central nervous system function through neural, endocrine, and immune pathways.
Objective: This comprehensive review synthesizes current evidence on the mechanistic relationships between gut microbial dysbiosis and psychiatric disorders, and critically evaluates microbiome-targeted therapeutic strategies including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions.
Methods: A narrative review was conducted using PubMed, PsycINFO, and Scopus databases, covering peer-reviewed literature from 2015 to 2025. Animal model studies, human clinical trials, and population-based observational studies were included.
Results: Substantial evidence links alterations in gut microbiota composition to depression, anxiety, schizophrenia, autism spectrum disorder, and neurodegenerative conditions. Psychobiotic interventions probiotics with demonstrated neuropsychiatric benefits — showed effect sizes comparable to conventional anxiolytics in randomized controlled trials, though study heterogeneity limits definitive conclusions. Dietary patterns, particularly the Mediterranean and plant-rich diets, were consistently associated with reduced depression risk via microbiome-mediated mechanisms.
Conclusion: The gut-brain axis represents a paradigm-shifting framework for understanding and treating mental illness. While promising, microbiome-based interventions require larger, longitudinal, and mechanistically rigorous clinical trials before integration into standard psychiatric care.

gut-brain axis, gut microbiome, mental health

1. Cryan, J. F., O'Riordan, K. J., Sandhu, K., Peterson, V., & Dinan, T. G. (2022). The gut microbiome in neurological disorders. The Lancet Neurology, 19(2), 179–194. [Google Scholar] [Crossref]

2. Dinan, T. G., Stanton, C., & Cryan, J. F. (2023). Psychobiotics: A novel class of psychotropic. Biological Psychiatry, 74(10), 720–726. [Google Scholar] [Crossref]

3. Kang, D. W., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., McDonough-Means, S., ... & Krajmalnik-Brown, R. (2022). Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota. Scientific Reports, 9(1), 1–12. [Google Scholar] [Crossref]

4. Rathore, S., Kamble, M., Farooqui, A., & Yadav, S. (2025). The bidirectional relationship between gut microbiome and mental health: A comprehensive review. Cureus, 17(3), e89441. [Google Scholar] [Crossref]

5. Jacka, F. N., O'Neil, A., Opie, R., Itsiopoulos, C., Cotton, S., Mohebbi, M., ... & Berk, M. (2017). A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial). BMC Medicine, 15(1), 23. [Google Scholar] [Crossref]

6. Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E. F., Wang, J., Tito, R. Y., ... & Raes, J. (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology, 4(4), 623–632. [Google Scholar] [Crossref]

7. Simpson, C. A., Diaz-Arteche, C., Eliby, D., Schwartz, O. S., Simmons, J. G., & Cowan, C. S. (2023). The gut microbiota in anxiety and depression: A systematic review. Clinical Psychology Review, 83, 101943. [Google Scholar] [Crossref]

8. Crumeyrolle-Arias, M., Jaglin, M., Bruneau, A., Vancassel, S., Cardona, A., Dauge, V., ... & Rabot, S. (2020). Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats. Psychoneuroendocrinology, 42, 207–217. [Google Scholar] [Crossref]

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