Transcutaneous auricular vagus nerve stimulation targets the brain-gut axis to treat functional dyspepsia: a scoping review of clinical evidence and mechanistic research
Abstract
Background Functional dyspepsia (FD) is a common gut–brain interaction disorder with suboptimal response to pharmacotherapy. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulation targeting the vagus nerve, has emerged as a promising brain–gut axis therapy. This scoping review (PRISMA-ScR, JBI methodology) synthesizes clinical and preclinical mechanistic evidence on taVNS for FD. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched up to December 20, 2025, following PRISMA-ScR. Using PICOS (adults with FD; taVNS; sham/non-vagal/active controls; symptoms, gastric function, psychological outcomes, biomarkers; RCTs/clinical trials and controlled animal studies), two reviewers independently screened, extracted data, and assessed bias (RoB2 for RCTs, SYRCLE for animal studies). A narrative synthesis was performed due to heterogeneity. Results Four RCTs (n = 480) and eight preclinical rodent studies met inclusion. All RCTs showed significant improvements in dyspeptic symptoms, gastric accommodation, slow-wave normalization, and comorbid anxiety, depression, sleep disturbance versus sham/non-vagal control, sustained for 4–12 weeks. Stimulation parameters varied (10–30 Hz; 0.5–10 mA; 2–4 weeks); risk of bias low-moderate. Preclinical rodent evidence supported five interconnected candidate mechanisms: (i) autonomic balance and cholinergic modulation; (ii) α7nAChR/NF-κB anti-inflammatory pathway with duodenal barrier restoration; (iii) NGF/TrkA/PLC-γ/TRPV1-mediated visceral hypersensitivity suppression; (iv) HPA axis inhibition; (v) rebalancing of brain-gut peptides (motilin, CCK, GLP-1). Conclusion This review characterizes taVNS as a safe, well-tolerated, mechanistically plausible non-invasive neuromodulation for FD acting on multiple brain–gut axis nodes. However, the small number of trials, parameter heterogeneity, and limited follow-up constrain definitive conclusions. Adequately powered, multicenter RCTs with standardized protocols and long-term follow-up are needed to confirm efficacy and define optimal regimens.