Prolonged Induction of Germfree Bile Acid Pattern in Conventional Rats by Antibiotics

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Abstract
Male conventional rats have been treated for five days with benzylpenicillin, neomycin, kanamycin, erythromycin, bacitracin+neomycin, succinylsulfathiazole or metronidazole. Total fecal bile acids were analyzed in samples collected during periods of three days during the pretreatment period and during the eight weeks following drug treatment. Metronidazole or succinylsulfathiazole had no or minor effects on the conventional bile acid pattern and the “bile acid index” (ratio β‐muricholic acid/deoxycholic acid) remained low. Benzylpenicillin, neomycin or kanamycin induced a germfree bile acid pattern, i.e. increased the relative amounts of α‐ and β‐muricholic acid in feces and eliminated deoxycholic acid and hyodeoxycholic acid from feces. The high bile acid index was normalized within three weeks after termination of drug treatment but the excretion of α‐ and β‐muricholic acid was not normalized until a normal flora had been established by giving an enema with intestinal contents from intact, conventional rats. Treatment with erythromycin or bacitracin+neomycin also produced a germfree bile acid pattern. In these cases, the bile acid index was not back to normal until after five to eight weeks and the excretion of the muricholic acids was not normalized until an enema with intestinal bacteria had been given. It is suggested that these long‐lasting effects of antibiotics on the metabolism of bile acids in the intestinal tract should be considered after short‐term antibiotic therapy in humans.