Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA.
Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA.
Toxicol Appl Pharmacol. 2014 Jun 1;277(2):138-45. doi: 10.1016/j.taap.2014.03.009. Epub 2014 Mar 20.
Antibiotic treatments have been used to modulate intestinal bacteria and investigate the role of intestinal bacteria on bile acid (BA) homeostasis. However, knowledge on which intestinal bacteria and bile acids are modified by antibiotics is limited. In the present study, mice were administered various antibiotics, 47 of the most abundant bacterial species in intestine, as well as individual BAs in plasma, liver, and intestine were quantified. Compared to the two antibiotic combinations (vancomycin+imipenem and cephalothin+neomycin), the three single antibiotics (metronidazole, ciprofloxacin and aztreonam) have less effect on intestinal bacterial profiles, and thus on host BA profiles and mRNA expression of genes that are important for BA homeostasis. The two antibiotic combinations decreased the ratio of Firmicutes to Bacteroidetes in intestine, as well as most secondary BAs in serum, liver and intestine. Additionally, the two antibiotic combinations significantly increased mRNA of the hepatic BA uptake transporters (Ntcp and Oatp1b2) and canalicular BA efflux transporters (Bsep and Mrp2), but decreased mRNA of the hepatic BA synthetic enzyme Cyp8b1, suggesting an elevated enterohepatic circulation of BAs. Interestingly, the two antibiotic combinations tended to have opposite effect on the mRNAs of most intestinal genes, which tended to be inhibited by vancomycin+imipenem but stimulated by cephalothin+neomycin. To conclude, the present study clearly shows that various antibiotics have distinct effects on modulating intestinal bacteria and host BA metabolism.
抗生素治疗已被用于调节肠道细菌，并研究肠道细菌在胆汁酸（BA）稳态中的作用。然而，关于抗生素修饰的肠道细菌和胆汁酸的知识有限。在本研究中，给小鼠施用了各种抗生素、肠道中最丰富的 47 种细菌物种，以及血浆、肝脏和肠道中的个体胆汁酸，定量检测了它们的含量。与两种抗生素组合（万古霉素+亚胺培南和头孢噻吩+新霉素）相比，三种单一抗生素（甲硝唑、环丙沙星和氨曲南）对肠道细菌谱的影响较小，从而对宿主 BA 谱和对 BA 稳态很重要的基因的 mRNA 表达影响较小。两种抗生素组合降低了肠道中厚壁菌门与拟杆菌门的比例，以及血清、肝脏和肠道中的大多数次级 BA。此外，两种抗生素组合显著增加了肝脏 BA 摄取转运体（Ntcp 和 Oatp1b2）和胆小管 BA 外排转运体（Bsep 和 Mrp2）的 mRNA，但降低了肝脏 BA 合成酶 Cyp8b1 的 mRNA，提示 BA 的肠肝循环增加。有趣的是，两种抗生素组合对大多数肠道基因的 mRNAs 具有相反的作用趋势，这些基因的 mRNAs 被万古霉素+亚胺培南抑制，而被头孢噻吩+新霉素刺激。总之，本研究清楚地表明，各种抗生素对调节肠道细菌和宿主 BA 代谢有不同的作用。
