The biosynthesis of ethyl lithocholate by fecal microorganisms

Abstract

The metabolism of [ 14COOH]-lithocholic acid anaerobically by heavy cell suspensions of Bacteroides fragilis ss thetaiotaomicron, (strains 6 and 11, respectively), Citrobacter sp. and Peptostreptococcus productus I resulted in the production of a neutral metabolite (2–5%) as determined by thin-layer chromatography. An 80-fold increase in the concentrated cell suspensions of citrobacter and unlabeled lithocholic acid gave an extract which was partially purified by Sephadex LH-20 chromatography. The neutral metabolite isolated from this purification had identical thin-layer and gas-liquid Chromatographic properties with those of authentic ethyl lithocholate, and combined gas-liquid chromatography-mass sectrometry data supported the structure for ethyl lithocholate and not its 3β-epimer.Further sudies have shown that the formation of ethyl lithocholate requires the presence of ethanol, concentrated cell suspensions and anaerobic growth conditions. Under these circumstances B. fragilis ss thetaiotaomicron (strain No. 6) can achieve a conversion of 15% of lithocholic acid to its ethyl ester, citrobacter 10% and P. productus I less than 1%. The ability of select strains of fecal microorganisms to esterify a toxic bile acid such as lithocholic acid represents a novel reaction which may enhance or reduce its toxicity and/or carcinogenic potential in the colon.