The vagus nerve as a neurovisceral interface: a comprehensive review

The vagus nerve is the longest cranial nerve and a key component of the autonomic nervous system, functioning as a neurovisceral interface between the brain and peripheral organs. Despite well-defined anatomy, the mechanisms underlying its integrative roles in cardiovascular, metabolic, and neuropsychiatric regulation remain incompletely understood. This narrative review synthesizes current evidence on the anatomical organization, physiological functions, and clinical relevance of the vagus nerve, focusing on cardiac autonomic control, gastrointestinal and metabolic regulation, the gut, brain axis, and vagus nerve stimulation. In the cardiovascular system, it interacts with sympathetic pathways within the cardiac plexus and intrinsic cardiac nervous system to regulate heart rate and conduction. In the gastrointestinal system, it coordinates motility, secretion, and metabolic homeostasis through nutrient- and hormone-sensitive pathways. Within the gut, brain axis, emerging evidence highlights rapid neuroepithelial signaling and microbiota-dependent modulation mediated by vagal circuits. The vagus nerve stimulation represents a promising therapeutic strategy for restoring autonomic balance, although challenges remain in fiber selectivity and clinical variability. Advances in multi-omics approaches are beginning to reveal the molecular heterogeneity of vagal neurons, but significant gaps persist due to limited human anatomical data. In conclusion, the vagus nerve functions as a multidimensional integrative system, and a deeper understanding of its structure and molecular organization is essential for developing precise neuromodulatory therapies.