Identification of Oxysterols in Human Bile and Pigment Gallstones

Background & Aims: Although cholesterol is the most abundant sterol in animal tissues, oxidized products of cholesterol (oxysterols) also occur in mammalian organs and blood and are cytotoxic, atherogenic, and carcinogenic. However, the presence of oxysterols in bile or gallstones has never been reported. Methods: Fresh human bile and gallstones were collected. Sterol content and structure were analyzed using gas chromatography/mass spectrometry (GC/MS). Bacterial DNA was extracted from human gallstones. Results: GC/MS identified cholesta-4,6-diene-3-one and cholest-4-ene-3-one, with several as yet unidentified oxysterols in bile and stone samples. Several plant and fungal sterols were also present in gallstones. When 102 human gallstones were analyzed for oxysterols, they were markedly higher (as percent of total sterols) in pigment gallstones, where bacterial DNA is most abundant. Conclusions: These observations suggest biliary oxysterols are associated with the presence of bacteria and may play a role in the pathogenesis of gallstones and biliary tract cancers.