title: Impact of 4-epi-oxytetracycline on the gut microbiota and blood metabolomics of Wistar rats.
abstract: The impact of 4-epi-oxytetracycline (4-EOTC), one of the main oxytetracycline (OTC) metabolites, on the gut microbiota and physiological metabolism of Wistar rats was analyzed to explore the dynamic alterations apparent after repeated oral exposure (0.5, 5.0 or 50.0 mg/kg bw) for 15 days as shown by 16S rRNA pyrosequencing and UPLC-Q-TOF/MS analysis. Both principal component analysis and cluster analysis showed consistently altered patterns with distinct differences in the treated groups versus the control groups. 4-EOTC treatment at 5.0 or 50.0 mg/kg increased the relative abundance of the Actinobacteria, specifically Bifidobacteriaceae, and improved the synthesis of lysophosphatidylcholine (LysoPC), as shown by the lipid biomarkers LysoPC(16:0), LysoPC(18:3), LysoPC(20:3), and LysoPC(20:4). The metabolomic analysis of urine samples also identified four other decreased metabolites: diacylglycerol, sphingomyelin, triacylglycerol, and phosphatidylglycerol. Notably, the significant changes observed in these biomarkers demonstrated the ongoing disorder induced by 4-EOTC. Blood and urine analysis revealed that residual 4-EOTC accumulated in the rats, even two weeks after oral 4-EOTC administration, ceased. Thus, through thorough analysis, it can be concluded that the alteration of the gut microbiota and disorders in blood metabolomics are correlated with 4-EOTC treatment.
authors.affiliation: College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Han
authors.affiliation: Hangzhou Institute for Food and Drug Control, Hangzhou 310004, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Xiao
authors.affiliation: College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Zhenmei
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D050356:Lipid Metabolism; D008297:Male; D055442:Metabolome; D010118:Oxytetracycline / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D017208:Rats, Wistar
chemical_list: C000619717:4-epi-oxytetracycline; D000900:Anti-Bacterial Agents; D015415:Biomarkers; D010118:Oxytetracycline