Intestinal barrier dysfunction in developing liver cirrhosis: An in vivo analysis of bacterial translocation

Transmucosal passage of bacteria across the intestine, the essential step for bacterial translocation, has been identified as a key event in the pathogenesis of life-threatening infections in cirrhosis. Existing animal models of liver cirrhosis only provide indirect information about the pathogenesis of such infections. The aim of this study has been to assess transmucosal passage and bacterial translocation directly in vivo using a rat model of developing liver cirrhosis.

Male Sprague Dawley rats were randomly assigned to two groups: controls and animals with developing liver cirrhosis induced by s.c. injection of carbon tetrachloride. In anesthetized animals a suspension of green fluorescent protein (GFP)-tagged E. coli was administered into the terminal ileum. Time intervals necessary for translocation of E. coli into the mucosa and muscularis were assessed by intravital microscopy and translocation of E. coli in mesentery, liver and spleen was determined microbiologically.

Bacterial kinetics at the level of the mucosa and muscularis showed significant enhancement in cirrhotic rats compared to the controls (P < 0.001). GFP-expressing E. coli were detected in the mesentery, liver and spleen of animals with cirrhosis taken one hour after E. coli administration. However, cultures of control animals remained sterile.

Intravital microscopy of fluorescent bacteria represents a novel approach to studying bacterial translocation in vivo. Here we report that this technique can be used to visualize bacterial transit in in vivo and gives further support to the transmucosal passage of bacteria across the intestine correlating with bacterial translocation in CCl(4)-induced liver cirrhosis.