Microbiota Dysbiosis and the Gut-Brain Axis in Psychiatric Disorders: Molecular Mechanisms, Clinical Evidence, and Therapeutic Perspectives
10 affiliations
- 1Department of Neuroscience, Head-Neck and Chest, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- 2Department of Neuroscience, Section of Psychiatry, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- 3Unit of Medical Genetics, Department of Laboratory Medicine, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy
- 4Spine Surgery Department, Bambino Gesù Children’s Hospital IRCCS, 00168 Rome, Italy
- 5Division of Gynecologic Oncology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- 6Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- 7Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- 8Breast Surgery Unit, Department of Woman and Child’s Health and Public Health Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- 9Department of Medical and Surgical Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy
- 10Unit of Internal Medicine, Cristo Re Hospital, 00167 Rome, Italy
Abstract
The gut-brain axis provides a biologically plausible framework for understanding the bidirectional interactions among the intestinal microbiota, immune-inflammatory signaling, neuroendocrine regulation, neurotransmitter metabolism, and psychiatric symptoms. Although numerous recent reviews have examined individual psychiatric disorders, microbial composition, or microbiota-targeted therapies, the field still lacks a sufficiently integrated appraisal that clearly distinguishes associative findings from human studies, mechanistic evidence from preclinical research, and preliminary clinical interventions. This structured narrative review synthesizes clinical, translational, and preclinical studies across major depressive disorder, bipolar disorder, anxiety disorders, schizophrenia, and trauma-related conditions. The main literature search covered publications from January 2015 to January 2026; earlier foundational mechanistic studies of key relevance to gut–brain communication were also considered. Recurrent pathways include altered short-chain fatty acid production, tryptophan-kynurenine metabolism, immune-inflammatory activation, hypothalamic-pituitary-adrenal axis dysregulation, neurotransmitter-related signaling, impaired intestinal and blood-brain barrier integrity, and vagus nerve-mediated communication. Human studies predominantly demonstrate associations between microbial signatures and psychiatric phenotypes, symptom severity, inflammatory status, or treatment response, whereas preclinical models provide stronger mechanistic evidence that microbiota manipulation can influence behavioral, neurochemical, immune, and neuroendocrine outcomes. Probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation show therapeutic potential; however, the current evidence is limited by small sample sizes, methodological heterogeneity, insufficient standardization, and a lack of long-term validation. The distinctive contribution of this review is its structured comparison of three levels of evidence—human observational findings, experimental mechanistic studies, and emerging clinical interventions—thereby clarifying what has been consistently replicated, what remains mechanistically plausible, and what is not yet ready for routine application in psychiatric practice.
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BibTeX
@article{marano2026microbiota,
title = {{Microbiota Dysbiosis and the Gut-Brain Axis in Psychiatric Disorders: Molecular Mechanisms, Clinical Evidence, and Therapeutic Perspectives}},
author = {Giuseppe Marano and Luca Conci and Leila Farsakh and Gianandrea Traversi and Osvaldo Mazza and Valentina Ricozzi and Silvia Rotondaro and Antonella Migliore and Esmeralda Capristo and Gianluca Franceschini and Eleonora Gaetani and Marianna Mazza},
journal = {Alpha Psychiatry},
year = {2026},
month = oct,
doi = {10.31083/ap54121},
url = {https://doi.org/10.31083/ap54121},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Microbiota Dysbiosis and the Gut-Brain Axis in Psychiatric Disorders: Molecular Mechanisms, Clinical Evidence, and Therapeutic Perspectives
AU - Giuseppe Marano
AU - Luca Conci
AU - Leila Farsakh
AU - Gianandrea Traversi
AU - Osvaldo Mazza
AU - Valentina Ricozzi
AU - Silvia Rotondaro
AU - Antonella Migliore
AU - Esmeralda Capristo
AU - Gianluca Franceschini
AU - Eleonora Gaetani
AU - Marianna Mazza
PY - 2026
DA - 2026/10/22
JO - Alpha Psychiatry
DO - 10.31083/ap54121
UR - https://doi.org/10.31083/ap54121
AB - The gut-brain axis provides a biologically plausible framework for understanding the bidirectional interactions among the intestinal microbiota, immune-inflammatory signaling, neuroendocrine regulation, neurotransmitter metabolism, and psychiatric symptoms. Although numerous recent reviews have examined individual psychiatric disorders, microbial composition, or microbiota-targeted therapies, the field still lacks a sufficiently integrated appraisal that clearly distinguishes associative findings from human studies, mechanistic evidence from preclinical research, and preliminary clinical interventions. This structured narrative review synthesizes clinical, translational, and preclinical studies across major depressive disorder, bipolar disorder, anxiety disorders, schizophrenia, and trauma-related conditions. The main literature search covered publications from January 2015 to January 2026; earlier foundational mechanistic studies of key relevance to gut–brain communication were also considered. Recurrent pathways include altered short-chain fatty acid production, tryptophan-kynurenine metabolism, immune-inflammatory activation, hypothalamic-pituitary-adrenal axis dysregulation, neurotransmitter-related signaling, impaired intestinal and blood-brain barrier integrity, and vagus nerve-mediated communication. Human studies predominantly demonstrate associations between microbial signatures and psychiatric phenotypes, symptom severity, inflammatory status, or treatment response, whereas preclinical models provide stronger mechanistic evidence that microbiota manipulation can influence behavioral, neurochemical, immune, and neuroendocrine outcomes. Probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation show therapeutic potential; however, the current evidence is limited by small sample sizes, methodological heterogeneity, insufficient standardization, and a lack of long-term validation. The distinctive contribution of this review is its structured comparison of three levels of evidence—human observational findings, experimental mechanistic studies, and emerging clinical interventions—thereby clarifying what has been consistently replicated, what remains mechanistically plausible, and what is not yet ready for routine application in psychiatric practice.
SN - 2757-8038
ER -