The urinary excretion of bacterial amino-acid metabolites by rats fed saccharin in the diet.

Administration of a diet containing 7.5% saccharin to adult male rats for 40 days caused a three- to four-fold increase in the daily excretion of indican and rho-cresol. Indican is formed from indole which is a microbial metabolite of tryptophan, whilst rho-cresol is formed by the gut flora from tyrosine. The excretion of phenol, which is also a microbial metabolite of tyrosine, was abolished by saccharin administration for 40 days. Analysis of urines collected at 13, 18 and 24 months during a two-generation cancer bioassay showed that these changes occur throughout the life of saccharin-treated rats. These data indicate that saccharin changes the metabolism of amino acids by the gut flora, leading to an increased formation of products known to have promoting or co-carcinogenic properties.