The Role of Extracellular Vesicles as Diagnostic Tools in Gut-Brain Axis Disorders

The gut-brain axis represents a dynamic two-way signaling network whose dysregulation has been implicated in a wide range of neurogastrointestinal disorders. In this context, extracellular vesicles (EVs) have emerged as critical mediators of intercellular signaling and as promising non-invasive biomarkers. Derived from host and microbial cells, EVs carry bioactive cargo-including proteins, lipids, nucleic acids, and metabolites-that reflect the physiological or pathological state of their cells of origin. Their ability to cross biological barriers, such as the blood-brain barrier, underscores their potential for diagnosing and monitoring gut-brain axis dysfunctions. In this mini-review, we integrate microbial and brain-derived EVs within the framework of gut-brain axis disorders and propose three translational "diagnostic niches": microbial EVs as systemic markers of dysbiosis and immune activation, brain-derived EVs as liquid biopsies of the central nervous system (CNS) pathology, and engineered or technologically captured EVs as platforms for point-of-care testing. We summarize recent mechanistic insights, highlight disease-specific evidence in irritable bowel syndrome, inflammatory bowel disease, neurodegenerative, and psychiatric conditions, and critically appraise emerging isolation and analytical technologies in light of MISEV2023 recommendations. Finally, we discuss current limitations and translational hurdles, outlining how standardized EV-based diagnostics may be incorporated into precision medicine strategies targeting neurogastrointestinal diseases.