TY - JOUR T1 - <strong>Urinary <strong>Bile Acids Profile of Cesarean Sectioned Newborns</strong><strong> is Characterized by Oxidative Metabolism of Primary Bile Acids:</strong><strong> Limited Roles of Fetal-specific CYP3A7 in Cholate Oxidations</strong><strong>.</strong></strong> JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.120.000011 SP - DMD-AR-2020-000011 AU - Wen-Xia Wang AU - Li Chen AU - Guo-Yu Wang AU - Jin-Ling Zhang AU - Xianwen Tan AU - Qiu-Hong Lin AU - Yu-Jie Chen AU - Jian Zhang AU - Ping-Ping Zhu AU - Jia Miao AU - Mingming Su AU - Changxiao Liu AU - Wei Jia AU - Ke Lan Y1 - 2020/01/01 UR - http://dmd.aspetjournals.org/content/early/2020/06/04/dmd.120.000011.abstract N2 - This work aims to investigate how the bile acid metabolism of newborns differs from that of adults along the axis of primary, secondary and tertiary bile acids (BAs). The total unconjugated BA profiles were quantitatively determined by enzyme-digestion techniques in urine of 21 cesarean sectioned newborns, 29 healthy parturient women, 30 healthy male and 28 healthy non-pregmant female. Due to lack of developed gut microbiota, newborns exhibited a poor metabolism of secondary BAs as expected. Accordingly, the tertiary BAs contributed limitedly to the urinary excretion of BAs in newborns despite that their tertiary-to-secondary ratios significantly increased. As a result, the primary BAs of newborns underwent extensive oxidation metabolism, resulting in elevated urinary levels of some fetal-specific BAs, including 3-dehydroCA, isoCA, 12-oxoCDCA and nine tetrahydroxy-cholan-24-oic acids (Tetra-BAs). Parturient women had significantly elevated urinary levels of tertiary BAs and fetal-specific BAs compared to female control, indicating that they may be excreted into amniotic fluid for maternal disposition. In vitro metabolism assay in infant liver microsomes showed that four Tetra-BAs and 3-dehydroCA were hydroxylated metabolites of cholate, glycocholate and particularly taurocholate. However, the recombinant P450 enzyme assay found that the fetal specific CYP3A7 did not contribute to these oxidation metabolisms as much as expected compared to CYP3A4. In conclusion, newborns show the BA metabolism pattern predominated by primary BA oxidations due to immaturity of secondary BA metabolism. Translational studies following this finding may bring new ideas and strategies for both pediatric pharmacology and diagnosis and treatment of perinatal cholestasis associated diseases. ER -