Transcutaneous vagal nerve stimulation protects against stress‐induced intestinal barrier dysfunction in healthy adults

BACKGROUND: Intestinal barrier dysfunction is the likely initiating event in multiple human diseases. Currently, there are limited therapeutic strategies to address its dysfunction. Animal studies suggest that vagal nerve stimulation may improve intestinal barrier function, but this has not been evaluated in humans. This study aimed to determine the effect of vagal nerve stimulation on intestinal permeability in adults administered a bolus dose of intravenous corticotropin releasing hormone (CRH) which has been shown to increase small intestinal permeability in healthy human subjects. METHODS: In a cross‐over study, 16 volunteers (median age 34 years, 11 female) were randomized to receive auricular transcutaneous vagal nerve or sham stimulation (10 minutes each side) after intravenous administration of 100 µg of CRH. Intestinal barrier function was measured before and 2 h after each intervention with dual‐sugar urine testing (lactulose:mannitol ratio) and intestinal fatty‐acid binding protein (I‐FABP). KEY RESULTS: Exposure to CRH increased I‐FABP concentrations by a median of 49 (IQR 4‐71)% (p = 0.009). Lactulose:mannitol ratios were 0.029 (0.025‐0.050) following vagal stimulation compared with 0.062 (0.032‐0.170) following sham stimulation (p = 0.0092), representing a fall of 53 (22‐71)%. I‐FABP concentrations did not change (p = 0.90). CONCLUSIONS: Brief non‐invasive vagal nerve stimulation consistently reduces paracellular permeability of the small intestine after CRH administration, but does not entirely mitigate I‐FABP release from the epithelium. Studies of vagal nerve stimulation in disease states are warranted.