Auricular Vagus Nerve Stimulation in Inflammatory Bowel Disease: Mechanistic Insights and Biomarker-Based Evaluation of Therapeutic Response

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by dysregulated host–microbiota interactions, epithelial barrier dysfunction, and aberrant immune activation. Despite advances in biologic and small-molecule therapies, a substantial proportion of patients exhibit incomplete response, loss of response, or treatment-related adverse effects, underscoring the need for novel adjunctive therapeutic approaches. The vagus nerve exerts a pivotal effects on immune homeostasis through the cholinergic anti-inflammatory pathway, thereby integrating peripheral immune sensing with central autonomic regulation. Within the context of IBD, a diminution in vagal tone has been observed to correlate with persistent mucosal inflammation and immune dysregulation. Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique that may activate vagal circuits and modulate neuroimmune signaling without surgical intervention. This review endeavors to critically evaluate the potential efficacy of ta-VNS in the context of IBD, with particular emphasis on its discernible effects on immune, epithelial barrier, microbiota-related, and autonomic biomarkers. Emerging evidence, stemming from preliminary investigations, suggests that ta-VNS may exert an influence on inflammatory cytokine profiles, epithelial tight junction integrity, gut microbial composition, and systemic autonomic balance, warranting further elucidation. In addition, the review discusses differential responses between Crohn’s disease and ulcerative colitis, summarizes current preclinical and clinical evidence, and highlights biomarker-based strategies for evaluating therapeutic response in future randomized controlled trials. Although current evidence remains preliminary and stimulation parameters are not yet standardized, ta-VNS represents a promising adjunctive neuroimmune modulation strategy in IBD.