Context-Dependent Modulation of Epithelial Barrier Integrity and Intestinal Permeability by Transcutaneous Auricular...

Inflammatory bowel disease, including ulcerative colitis (UC) and Crohn's disease (CD), is associated with reduced vagus nerve activity and impaired barrier function. Transcutaneous auricular vagus nerve stimulation (taVNS) shows preventive effects in acute colitis, but its impact on intestinal barrier integrity remains unclear. To assess this, C57BL/6 male mice received taVNS (10 V, 20 Hz, 500 µs, 10 min) prior to colitis induction. UC-like colitis was induced using 5% dextran sulfate sodium (DSS) for 120 h with daily taVNS, while CD-like colitis was induced by intrarectal dinitrobenzene sulfonic acid (DNBS, 4 mg) in 30% ethanol with taVNS during induction and for 48 h. TaVNS reduced colonic proliferation in non-colitic mice in a homeostatic manner, as well as in DNBS-colitic mice, and enhanced differentiation. It decreased enteroendocrine cells in non-colitic conditions but not in DSS-colitic mice, and reduced tuft cells in DSS and DNBS groups. TaVNS increased MUC2 in DSS colitis and decreased TFF3 in DNBS controls. It decreased Lgr5⁺ stem cells in DSS controls but maintained them during DSS colitis, while HOPX⁺ stem cells decreased in non-colitic DSS conditions, and fetal-like stem cells remained unchanged. Disease activity index negatively correlated with chromogranin A. TaVNS prevented increased paracellular permeability in the distal colon of DSS-colitic mice, increased TEER in distal DSS controls and proximal colitic colon, and enhanced ion transport in the proximal colon under non-colitic DSS conditions. Overall, taVNS effects on epithelial composition and barrier function are context- and model-dependent.