Small-bowel bacterial overgrowth and systemic immunosuppression in experimental peritonitis

The effect of intraperitoneal infection on small-bowel flora and on systemic immunity was studied in a rat model, with use of the delayed-type hypersensitivity (DTH) response to keyhole limpet hemocyanin (KLH) as a measure of global immunologic integrity. Twenty-four hours after the induction of peritonitis by cecal ligation and puncture, concentrations of Escherichia coli in the proximal gastrointestinal tract increased from fewer than 10(3) colony-forming units (CFU)/ml to more than 10(9) CFU/ml, and the DTH response decreased from 10.0 +/- 0.2 to 2.1 +/- 0.4 mm. To assess the contribution of this altered luminal flora to the observed suppression of DTH scores, cecal ligation without puncture was performed in a group of animals whose endogenous flora had been suppressed by administration of oral neomycin. Oral administration of live antibiotic-resistant E. coli to the study animals resulted in significant DTH depression compared with controls given saline solution (2.7 +/- 0.4 vs 4.4 +/- 0.4 mm, p less than 0.005), even though the gastrointestinal tract was anatomically intact. Similar depression was seen if the challenge was limited to the small bowel as a result of the prior performance of an ileostomy and occurred in the absence of significant systemic or portal levels of viable bacteria. The results suggest that gut endotoxin plays a role in the immunosuppression associated with peritonitis.