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

Area of Science:

• Gastroenterology
• Burn Injury Research
• Epithelial Biology

Background:

• Major burn injury induces systemic inflammation and metabolic changes.
• Early intestinal barrier failure exacerbates post-burn inflammation and organ dysfunction.
• The precise epithelial lesions causing focal leakage post-burn remain unclear.

Purpose of the Study:

• To characterize dynamic epithelial lesions, specifically villus-tip shedding, gap formation, and tracer leak sites, early after burn injury.
• To investigate the in vivo mechanisms of intestinal barrier disruption following major burns.

Main Methods:

• Utilized intravital multiphoton fluorescence microscopy in a mouse model of major burn injury (30-35% total body surface area).
• Assessed intestinal permeability using fluorescein isothiocyanate-dextran and portal venous sampling at 2, 4, and 6 hours post-burn.
• Quantified villus shedding dynamics, epithelial gap density, goblet cell proportion, and focal tracer leak sites in the distal ileum.

Main Results:

• Burn injury significantly shortened shedding duration and increased shedding prevalence, with a shift towards a condensation-first pattern.
• Increased epithelial gap density and goblet cell proportion were observed post-burn.
• Elevated tracer concentrations in portal serum at 6 hours correlated with focal epithelial defects and incomplete sealing.

Conclusions:

• Major burns rapidly disrupt intestinal barrier integrity via accelerated stress-associated shedding and increased gap formation.
• These time-resolved structural lesions contribute to early hyperpermeability after burn injury.
• Identified a time-critical window for gut-directed interventions to mitigate downstream post-burn complications.