Dysregulated Epithelial Shedding Promotes Early Intestinal Hyperpermeability Following Major Burn Injury.

A major burn injury triggers systemic inflammation and metabolic responses beyond the skin. Early intestinal barrier failure can amplify postburn inflammation and organ dysfunction, yet the dynamic epithelial lesions that generate focal leakage in vivo remain unclear. We characterized villus-tip epithelial shedding, epithelial gap formation, and tracer leak sites early after burn injuries using intravital multiphoton fluorescence microscopy. Male C57BL/6 mice were assigned to control or burn groups (30%-35% total body surface area full-thickness burn; n = 6/group). Intestinal permeability was assessed at 2, 4, and 6 h postinjury using luminal fluorescein isothiocyanate-dextran (4 kilodaltons) with portal venous sampling. Distal-ileum intravital imaging was performed 330-420 min postinjury (at 1-min intervals). Ten villi per mouse were quantified for shedding duration and prevalence, a condensation-first vs extrusion-first sequence, epithelial gap density, goblet-cell proportion, and focal luminal tracer leak sites. A major burn shortened shedding duration and increased shedding prevalence during the 90-min observation (P < .05), with a shift toward a condensation-first pattern and fewer extrusion-first events (P < .05). Burn increased epithelial gap density and goblet-cell proportion (P < .05). Portal serum fluorescein isothiocyanate-dextran concentrations were elevated at 6 h (P < .05), and imaging localized tracer penetration to discrete postshedding epithelial defects, consistent with incomplete sealing. Major burn rapidly disrupts intestinal barrier integrity through accelerated stress-associated shedding, increased gap formation, and focal leak sites. These time-resolved structural lesions provide an in vivo substrate for early hyperpermeability and suggest a time-critical window for gut-directed interventions to mitigate downstream postburn complications.