The biosynthesis of ethyl esters of lithocholic acid and isolithocholic acid by rat intestinal microflora

Abstract

Recent reports concerning the tumor-promoting action of lithocholic acid in the colon and liver suggest that the metabolism of this major fecal bile acid may be important in carcinogenesis at various target sites. The metabolism of [ 14COOH]-lithocholic acid by rat intestinal microflora derived from standard laboratory chow-fed animals produced slightly more non-polar metabolites than those incubations which utilized flora from animals on a high lean-beef regimen. Purification of the crude bacterial extracts by Sephadex LH-20 chromatography and analysis of the radioactive peaks by glass fiber paper chromatography resulted in the identification of two neutral metabolites. Confirmation of their identity as ethyl lithocholate and ethyl isolithocholate was achieved by gas-liquid chromatography and combined gas-liquid chromatography-chemical ionization mass spectrometry. The formation of ethyl esters of lithocholic acid and isolithocholic acid by the intestinal microflora requires the presence of ethanol and anaerobic incubation conditions. These data support results obtained previously with single human fecal microorganisms. Since the formation of these derivatives in vitro occurs under anaerobic conditions only, it is possible that such derivatives may form physiologically in the colon. The carcinogenic potential of these derivatives is under investigation.