The Microbiome-Gut-Brain Axis: A Review on Novel Insights into Pathophysiology and Targeted Therapy of Neurological Disorders

Abstract

Background: Microorganisms, as ancient inhabitants of Earth, play a pivotal role in human evolution and physiological function. Among their various interactions, the gut microbiome-brain axis has emerged as a complex, bidirectional communication network between the gastrointestinal tract and the central nervous system. Over the past two decades, this axis has become a focal point of interdisciplinary research. Methods: This review study investigated the gut-brain microbiome axis. Through a comprehensive search of national and international databases (2015-2025), the inclusion criteria consisted of: 1) review studies on the gut-brain microbiome axis, 2) clinical research examining the impact of microbiome on the nervous system, 3) systematic reviews of pathogenetic mechanisms, and 4) studies on treating neurological disorders through gut-brain interventions. From an initial pool of 147 articles, 112 met the eligibility criteria after screening, with 100 articles ultimately included in the final analysis. Findings: The analysis revealed that gut microbial dysbiosis is significantly associated with a broad spectrum of neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis (MS), autism spectrum disorders, and depression. These findings not only underscore the microbiome's critical role in neuropathophysiology but also propose novel approaches for targeted therapeutic interventions. Conclusion: This review study demonstrated that modulating the gut microbiome through novel therapeutic approaches, such as next-generation probiotics, fecal microbiota transplantation (FMT), and targeted dietary interventions, can serve as promising strategies for managing neurological disorders. Additionally, the study provides a conceptual framework for future research aimed at discovering microbiome-based biomarkers and designing personalized treatment protocols. © 2026, Isfahan University of Medical Sciences(IUMS). All rights reserved.