Shedding-induced gap formation contributes to gut barrier dysfunction in endotoxemia

Area of Science:

• Gastroenterology
• Cell Biology
• Immunology

Background:

• The intestinal lining rapidly renews cells to maintain barrier integrity.
• Conditions like sepsis and burns disrupt this balance, causing barrier dysfunction.
• Detailed changes in intestinal villi during barrier dysfunction remain unclear.

Purpose of the Study:

• To investigate the impact of endotoxemia on intestinal villi structure and barrier function.
• To analyze cellular dynamics and identify mechanisms of gut barrier disruption.

Main Methods:

• Intestinal barrier dysfunction was induced using lipopolysaccharide (LPS) in C57BL/6 mice.
• Intravital multiphoton microscopy captured cellular dynamics in the small intestine.
• Epithelial cell shedding, gap formation, and intestinal leaks were quantitatively analyzed.

Main Results:

• Endotoxemia (LPS) increased intestinal epithelial cell shedding and gap formation.
• LPS-induced shedding led to significant intestinal leaks through gaps and paracellular spaces.
• While total leaks increased, the proportion of leaks through gaps versus paracellular spaces remained similar to controls.

Conclusions:

• Endotoxemia impairs gut barrier function by increasing epithelial shedding, gap formation, and intestinal leaks.
• The distribution of leaks between gaps and paracellular spaces is minimally affected by local barrier maintenance impairment.