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

Abstract

Male conventional rats were treated for 5 days with benzylpenicillin, neomycin, kanamycin, erythromycin, bacitracin + neomycin, succinylsulfathiazole or metronidazole. Total fecal bile acids were analyzed in samples collected during periods of 3 days during the pretreatment period and during the 8 wk following drug treatment. Metronidazole or succinylsulfathiazole had minor or no effects on the conventional bile acid pattern and the bile acid index (ratio .beta.-muricholic acid/deoxycholic acid) remained low. Benzylpenicillin, neomycin or kanamycin induced a germfree bile acid pattern, i.e., increased the relative amounts of .alpha.- and .beta.-muricholic acid in feces and eliminated deoxycholic acid and hyodeoxycholic acid from feces. The high bile acid index was normalized within 3 wk after termination of drug treatment but the excretion of .alpha.- and .beta.-muricholic acid was not normalized until a normal flora was 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 5-8 wk and the excretion of the muricholic acids was not normalized until an enema with intestinal bacteria was given. 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.