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KMID : 0043320120350111969
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Archives of Pharmacal Research
2012 Volume.35 No. 11 p.1969 ~ p.1977
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vMAlteration of bile acid metabolism in pseudo germ-free rats
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Bhowmik Salil Kumar
An Ji-Hye
Lee Soo-Hyun
Jung Byung-Hwa
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Abstract
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To characterize the impact of gut microbiota on host bile acid metabolism, we investigated the metabolic profiles of oxysterols and bile acids (BAs) in a conventional rat model (SD) (n=5) and its pseudo germ-free (GF) equivalent (n=5). GF rats were developed by the oral administration of bacitracin, neomycin and streptomycin (200 mg/kg, each) twice a day for 6 days. Urinary levels of oxysterols and bile acid metabolites were quantified using gas chromatography-mass spectrometry (GC-MS). The activity levels of enzymes involved in the bile acid metabolic pathway were determined through urinary concentration ratio between product to precursor. Cholic acid (CA) and α-/β-muricholic acid (α-/β-MCA) were significantly elevated at pseudo germ-free condition. An increase of hydroxylase (cholesterol 7α-hydroxylase, oxysterol 7α-hydroxylase and cytochrome P450 scc) and a significant decrease of 7α-dehydroxylase were observed. The urinary concentration ratio of primary bile acids, a marker for hepatotoxicity, increased in pseudo germfree conditions. Therefore, it was found that gut microbiota could play a significant role in the bile acids homeostasis and metabolism.
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KEYWORD
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Pseudo germ-free rat, Bile acids, Oxysterol, Gas chromatography-mass spectrometry, Liver toxicity
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