Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea.
Arch Pharm Res. 2012 Nov;35(11):1969-77. doi: 10.1007/s12272-012-1114-7. Epub 2012 Dec 4.
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.
为了研究肠道微生物群对宿主胆汁酸代谢的影响，我们研究了常规大鼠模型（SD）（n=5）及其假无菌（GF）等效物（n=5）中氧化固醇和胆汁酸（BA）的代谢谱。通过每天两次口服 200mg/kg 的杆菌肽、新霉素和链霉素（各 200mg/kg），6 天时间开发出了 GF 大鼠。使用气相色谱-质谱法（GC-MS）定量尿中氧化固醇和胆汁酸代谢物的水平。通过产物与前体的尿浓度比来确定参与胆汁酸代谢途径的酶的活性水平。在假无菌条件下，胆酸（CA）和α-/β-鼠胆酸（α-/β-MCA）的水平显著升高。观察到羟化酶（胆固醇 7α-羟化酶、氧化固醇 7α-羟化酶和细胞色素 P450scc）增加，7α-脱羟酶显著减少。初级胆汁酸的尿浓度比（肝毒性标志物）在假无菌条件下增加。因此，发现肠道微生物群可能在胆汁酸的动态平衡和代谢中发挥重要作用。
