Severe and prolonged states of catabolic stress have been shown to have profound effects on the intestinal tract microflora and intestinal function. Gut-derived sepsis is a term used to describe a state of systemic inflammation with organ dysfunction after severe catabolic stress hypothesized to be initiated and perpetuated by the intestinal tract microflora. Popular notions of the mechanism of this process have suggested that stress promotes the translocation of intestinal bacteria or their toxins into the systemic compartment resulting in the release of proinflammatory cytokines which participate in the systemic inflammatory response syndrome. This review is an attempt to redefine the mechanism of gut-derived sepsis by focusing on molecular events that result from host-pathogen interactions within the intestinal tract itself. This evidence-based review posits that gut-derived bacteremia, even with potent nosocomial pathogens, is an event of low proinflammatory potential and, itself, is an insufficient stimulus for the systemic inflammatory response and organ failure state typically seen after severe and prolonged catabolic stress. Mechanisms of this apparent paradox are discussed.

ObjectiveTo examine the effect of Pseudomonas aeruginosa on intestinal barrier function and its lethal potential when introduced into the intestinal tract of mice. Summary Background DataThe mere presence of P. aeruginosa in the intestinal tract of critically ill patients is associated with a threefold increase in death compared with matched cohorts without this pathogen. Whether this effect is a cause or a consequence of the critically ill state has not been previously addressed. MethodsTransepithelial electrical resistance, a measure of tight junction permeability, was evaluated in Caco-2 intestinal epithelial cells cells apically inoculated with live P. aeruginosa, exotoxin A, or purified PA-I lectin, an adhesin of P. aeruginosa. Lethality studies to P. aeruginosa were carried out in mice undergoing 30% surgical hepatectomy by injecting the bacteria or its various components directly into the cecum.

Although indigenous bacteria intimately colonize the intestinal mucosa, under normal conditions the intestinal epithelial cell is free of adherent bacteria. Nonetheless, commensal bacteria such asEscherichia coli adhere to and translocate across the intestinal epithelium in association with a number of pathologic states including hemorrhagic shock, immunosuppression, traumatic tissue injury, and lack of enteral feedings. The adhesins involved in the adherence of indigenous E. coli to the intestinal epithelium in vivo following catabolic stress are unknown. We have developed a mouse model to study the bacterial adhesins which mediate the increased intestinal adherence of E. coliafter partial hepatectomy and short-term starvation. Our studies demonstrated that hepatectomy and starvation in the mouse were associated with a 7,500-fold increase in the numbers of E. coli bacteria adhering to the cecum. In addition, erythrocyte agglutination studies, as well as immunostaining of fimbrial preparations and electron micrographs of the bacteria, revealed that surface type 1 fimbriae were more abundant in the commensal E. coli harvested from the ceca of the stressed mice. These E. coli isolates adhered to a mouse colon cell line and injected cecal loops in a mannose-inhibitable manner, which suggests a role for type 1 fimbriae in the adherence of the E. coli isolates to the cecum in vivo following host catabolic stress.