Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery

Area of Science:

• Gastroenterology
• Surgical Inflammation
• Gut Microbiome Research

Background:

• Postoperative ileus significantly delays gastrointestinal transit.
• The cause of this delay is debated: a physical barrier or inflammation.
• The role of gut-derived endotoxin in postoperative intestinal dysfunction is unclear.

Purpose of the Study:

• To investigate muscularis inflammation and endotoxin as causes of postoperative ileus.
• To determine if colonic manipulation causes distant small intestinal inflammation.
• To evaluate the mechanistic role of gut-derived endotoxin in postoperative intestinal dysfunction.

Main Methods:

• Surgical manipulation of the colon in rats with ileostomy.
• Analysis of isolated gastrointestinal transit.
• Investigation of intracolonic particle (LPS, microspheres) emigration into the intestinal muscularis.
• Quantification of mediator mRNA induction and leukocyte infiltrates.
• Assessment of in vitro small intestinal circular muscle contractility.

Main Results:

• Colonic manipulation delayed small intestinal transit, associated with leukocyte recruitment and inflammation in the small intestinal muscularis.
• Intracolonic LPS and microspheres transferred into the intestinal muscularis.
• Small intestinal muscle contractility was impaired postoperatively.
• Gut decontamination and TLR-4 deletion mitigated inflammation and prevented muscle dysfunction.

Conclusions:

• Selective colonic manipulation triggers a distant inflammatory response in the small intestinal muscularis, contributing to postoperative ileus.
• Gut-derived bacterial products are mechanistically involved in initiating this remote inflammatory cascade.