Involvement of the intestinal microflora in the formation of sulphur-containing metabolites of caffeine

The urine of conventional and germ-free rats was examined, after an oral dose of caffeine, with regard to the presence of sulphur-containing conjugates of this compound. 2. Only the methyl sulphoxide analogue was detected. 3. The ratio of the quantities of this metabolite in conventional and germ-free rat urine was 42:1. 4. The proposed mechanism for the formation of the methyl sulphoxide analogue of caffeine involves the biliary excretion of a mercapturic acid pathway metabolite of caffeine with subsequent metabolism by the intestinal microflora.