Intraperitoneal microbial contamination drives post-surgical peritoneal adhesions by mesothelial EGFR-signaling

Area of Science:

• Surgical pathology
• Cell biology
• Microbiology

Background:

• Peritoneal adhesions are common, costly complications of abdominal surgery.
• Current understanding of adhesion formation mechanisms is incomplete, with no existing cures.
• Adhesions cause significant morbidity, including intestinal obstruction, pain, and infertility.

Purpose of the Study:

• To elucidate the cellular origins and molecular drivers of post-surgical peritoneal adhesion formation.
• To investigate the role of gut microbial contamination in adhesion development.
• To identify potential therapeutic targets for adhesion prevention.

Main Methods:

• Genetic lineage tracing in mice to track myofibroblast origins.
• Analysis of epidermal growth factor receptor (EGFR) signaling pathways.
• In vivo studies involving EGFR inhibition in a murine adhesion model.
• Histological and molecular analysis of human adhesion tissues and mesothelium.

Main Results:

• Gut microbial contamination was shown to increase post-surgical adhesion formation.
• Adhesion myofibroblasts were identified to originate from the mesothelium.
• EGFR signaling, driven by specific ligands, was found to be crucial for this mesothelial transformation.
• EGFR inhibition significantly reduced adhesion formation in mice.
• Human adhesions showed enrichment of EGFR-positive cells of mesothelial origin, with increased mesothelial EGFR expression during bacterial peritonitis.

Conclusions:

• Bacterial contamination promotes peritoneal adhesion formation via mesothelial EGFR signaling.
• Targeting EGFR signaling represents a promising therapeutic strategy for preventing post-surgical adhesions.
• This study reveals a key mechanism linking microbial exposure to adhesion pathogenesis.