DOI: 10.1177/10738584261464980 ISSN: 1073-8584

Vagus Nerve Modulation of the Gut–Brain Axis: Implications for Mental Health and Cognitive Function

Diana Álvarez-Mejía, Guido Mascialino, Jose E. Leon-Rojas

The vagus nerve constitutes a core bidirectional pathway linking the central nervous system with peripheral organs and plays a fundamental role in gut–brain communication. Beyond its classical autonomic functions, accumulating evidence positions vagal signaling as a candidate integrative mechanism through which visceral, immune, and microbial inputs may modulate stress regulation, affective processing, cognition, and neuroplasticity. This narrative review synthesizes current anatomical and physiological knowledge of vagal pathways, with emphasis on afferent projections to the nucleus tractus solitarius and downstream modulation of noradrenergic, serotonergic, and cholinergic circuits involving the locus coeruleus, hippocampus, and prefrontal cortex. We further examine vagus nerve stimulation, including invasive and noninvasive approaches, as a neuromodulatory strategy for neurological and psychiatric disorders. Evidence is reviewed for its effects in epilepsy, mood and anxiety disorders, cognitive impairment, and neurodegenerative conditions, highlighting mechanisms such as synaptic plasticity enhancement, neuroimmune modulation, and regulation of hypothalamic–pituitary–adrenal axis activity. While findings support the translational relevance of vagal modulation, variability in stimulation parameters and outcome measures limits cross-study comparison. Greater methodological standardization and integration of neurocognitive endpoints are required to clarify its clinical and neuroscientific significance.

More from our Archive