Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice |
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Authors: | Youcai Zhang Pallavi B. Limaye Helen J. Renaud Curtis D. Klaassen |
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Affiliation: | Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA |
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Abstract: | 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. |
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Keywords: | Abca1, ATP-binding cassette transporter a1 BA, bile acid CA, cholic acid Bsep, bile salt-export pump CDCA, chenodeoxycholic acid Cyp, cytochrome P450 DCA, deoxycholic acid Fxr, farnesoid X receptor GAPDH, glyceraldehyde 3-phosphate dehydrogenase HDCA, hyodeoxycholic acid IS, internal standard LCA, lithocholic acid MCA, muricholic acid MDCA, murideoxycholic acid Mrp, multidrug resistance-associated protein Ntcp, sodium taurocholate cotransporting polypeptide Oatp/OATP, organic anion transporting polypeptide Ost, organic solute transporter 7-oxoDCA, 7-oxo-deoxycholic acid Shp, small heterodimer partner TCA, tauro-cholic acid T-12-epiDCA, tauro-12-epi deoxycholic acid UDCA, ursodeoxycholic acid UPLC, ultra performance liquid chromatography WT, wild type |
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