Table 2_Transcutaneous auricular vagus nerve stimulation targets the brain-gut axis to treat functional dyspepsia: a scoping review of clinical evidence and mechanistic research.docx

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).</p>Conclusion<p>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.</p>