Role of intestinal barrier in pathogenesis of pigment gallstone in a guinea pig model.

BACKGROUND: The function of the intestinal barrier has drawn more and more attention from researchers in recent years for its important role in many diseases such as burns, wounds, and pancreatitis. In our experimental studies on pigment gallstone, we found potential relationships between the function of the intestinal barrier and pigment gallstone formation. This study was undertaken to investigate the possible action and mechanism of the function of the intestinal barrier in the pathogenesis of pigment gallstone. METHODS: Eighty guinea pigs were divided into a normal group (CON), a pigment gallstone group (PS) and an intestinal mucosa protection group (GLN). Normal forage, pigment gallstone-forming forage and pigment gallstone-forming forage with supplemental intestinal mucosa protector (glutamine) were given to each group. In the gallstone-forming rate, morphology of intestinal mucosa, intestinal permeability, serum endotoxin and biliary beta-glucuronidase were assessed after 8 weeks. RESULTS: The rate of gallstone-formation was 73.9% in the PS group. Damage of intestinal mucosa, endotoxemia (from 77+/-43 X 10(-6) EU/L to 1,367+/-525 X 10(-6) EU/L, P<0.01) and increased activity of biliary beta-glucuronidase (endogenous beta-glucuronidase from 122.1+/-39.5 to 209.8+/-47.5 Fishman Unit, P<0.01, and exogenous beta-glucuronidase from 573.5+/-476.9 to 2,206.6+/-983.9 Fishman Unit, P<0.01) were observed in the PS group compared with the CON group. The rate gallstone-formation decreased significantly to 44.4% and the other indices except beta-glucuronidase were lower in the GLN group than in the PS group. CONCLUSIONS: The function of the intestinal barrier is correlated with pigment gallstone formation. Dysfunction of the intestinal barrier function may promote pigment gallstone formation through bacterial translocation, endotoxemia, and biliary beta-glucuronidase.