Effects of diet on glucaric acid concentration in bile and the formation of calcium bilirubinate gallstones

Abstract

The authors reported previously that beta-glucuronidase in bile, especially during biliary infection with Escherichia coli, plays a substantial role in producing cium bilirubinate gallstones. In the present study, bile levels of glucaro-1:4-lactone (measured as glucaric acid) the leading inhibitor of beta-glucuronidase, were measured in both man and in rats fed high, medium, and low protein-fat diets. Glucaric acid and total bilirubin in bile correlated well in human controls but not in gallstone patients. In animal experiments, the levels of these substances in bile were high in rats on high protein-high fat and low in those on low protein-low diets. These data suggest that when bile is infected with E. coli, calcium bilirubinate gallstones seemed to form more easily in patients on low protein-low fat diet than in those consuming food rich in protein and fat. On the other hand, the ratio of lecithin to cholesterol was higher in low protein-low fat rats than in high protein-high fat rats, suggesting that cholesterol gallstones were more likely to form on the latter diet. The animal, clinical, epidemiological, and dietary data are consistent with the known trend to a decreased incidence of calcium bilirubinate and an increased incidence of cholesterol gallstones in Japan.