vMAlteration of bile acid metabolism in pseudo germ-free rats

Authors
Bhowmik, Salil KumarAn, Ji HyeLee, Soo HyunJung, Byung Hwa
Issue Date
2012-11
Publisher
PHARMACEUTICAL SOC KOREA
Citation
ARCHIVES OF PHARMACAL RESEARCH, v.35, no.11, pp.1969 - 1977
Abstract
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 alpha-/beta-muricholic acid (alpha-/beta-MCA) were significantly elevated at pseudo germ-free condition. An increase of hydroxylase (cholesterol 7 alpha-hydroxylase, oxysterol 7 alpha-hydroxylase and cytochrome P450 scc) and a significant decrease of 7 alpha-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.
Keywords
CHROMATOGRAPHY-MASS SPECTROMETRY; NUCLEAR RECEPTORS; GUT MICROBIOME; HOST; MOUSE; SERUM; 7-ALPHA-DEHYDROXYLATION; ANTIBIOTICS; REPRESSES; ENERGY; CHROMATOGRAPHY-MASS SPECTROMETRY; NUCLEAR RECEPTORS; GUT MICROBIOME; HOST; MOUSE; SERUM; 7-ALPHA-DEHYDROXYLATION; ANTIBIOTICS; REPRESSES; ENERGY; Pseudo germ-free rat; Bile acids; Oxysterol; Gas chromatography-mass spectrometry; Liver toxicity
ISSN
0253-6269
URI
https://pubs.kist.re.kr/handle/201004/128677
DOI
10.1007/s12272-012-1114-7
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KIST Article > 2012
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