Supplemental Table S1-S5

All animal procedures were reviewed and approved by the Animal Care and Use Committee and were carried out in accordance with the Sichuan Agricultural University. A In consideration of the dysregulation of BA homeostasis was mainly occurred during the second or third trimester of pregnancy, this study was conducted from day 60 of gestation (G60) till farrowing (L0). VAN group was orally administered with vancomycin (20mg/kg diet), which was mixed with corn starch to 10 gram, from G60 to G114, while the control group (CON) orally received 10 gram corn starch. The feed intake from G60 to G90 was 2.45kg/d and thereafter 3.06kg/d. Blood samples of pregnant sows were collected from precaval vein every 7 to 8 days via catheters implanted at cephalic vein or via ear vein when catheters didn’t work after 12-hours fasting. In consideration of the barely faeces found at L0, maternal faeces were collected at G60, G90 and G105, respectively. Placental tissues, ileum tissues and fetal blood (umbilical cord vein) samples were collected after 8-hours fasting at G60 and G90, respectively, when pregnant swine were laparotomized and under deep isoflurane-induced anesthesia, and during parturition. Primary pig hepatocytes were isolated from 2~5 day old female pigs using 2-step perfusion method with a minor modification. Cell concentration was determined and 1.5 105 per well were plated in 24-well plates or 5 105 per well were plated in 6-well plates. Cells were grown in complete medium containing DMEM medium, 2.5% dextran-coated, charcoal-stripped fetal bovine serum. The total BA (TBA) was measured by the enzymatic cycling method assay kits in Model 3100 automatic biochemical analyzer (Hitachi, Tokyo, Japan). Bile acids profile was measured by UPLC-MS/MS. Estradiol was measured by estradiol radioimmunoassay KIT according to the manufacturer’s specifications.

所有动物实验程序均经动物护理与使用委员会（Animal Care and Use Committee）审查批准，并严格按照四川农业大学（Sichuan Agricultural University）的相关规范实施。鉴于胆汁酸（bile acids, BA）稳态失衡主要发生于妊娠第2或第3妊娠三月期，本研究于妊娠第60天（G60）至分娩当日（L0）期间开展。试验组（VAN组）自妊娠第60天至第114天，经口给予万古霉素（vancomycin，20mg/kg日粮），将其与10g玉米淀粉（corn starch）混合后给药；对照组（CON组）则经口给予等量10g玉米淀粉。妊娠第60天至第90天期间，受试母猪的日采食量为2.45kg/天，妊娠第90天之后调整为3.06kg/天。妊娠母猪的血液样本采集方式如下：通过头静脉（cephalic vein）植入导管后，每7~8天经腔前静脉（precaval vein）采集血液样本；若导管失效，则于禁食12小时后经耳静脉（ear vein）采集样本。鉴于分娩当日（L0）几乎无法采集到母猪粪便，故分别于妊娠第60天、第90天及第105天采集母猪粪便样本。分别于妊娠第60天和第90天，对禁食8小时后的妊娠母猪实施剖腹手术并采用深度异氟烷（isoflurane）诱导麻醉，采集胎盘组织、回肠（ileum）组织样本以及胎儿脐静脉（umbilical cord vein）血液样本；分娩过程中同样采集上述样本。采用改良两步灌流法（2-step perfusion method），从2~5日龄雌性仔猪体内分离得到猪原代肝细胞（primary pig hepatocytes）。完成细胞浓度测定后，以1.5×10^5个/孔的密度接种于24孔板，或以5×10^5个/孔的密度接种于6孔板。细胞于含DMEM培养基（DMEM）、2.5%葡聚糖包裹活性炭吸附胎牛血清（dextran-coated, charcoal-stripped fetal bovine serum）的完全培养基中培养。采用日立3100型全自动生化分析仪（Model 3100 automatic biochemical analyzer，Hitachi, Tokyo, Japan），通过酶循环法检测试剂盒（enzymatic cycling method assay kits）测定总胆汁酸（total BA, TBA）含量。胆汁酸谱采用超高效液相色谱-串联质谱法（UPLC-MS/MS）进行检测。雌二醇含量采用雌二醇放射免疫检测试剂盒（estradiol radioimmunoassay KIT），按照试剂盒说明书进行测定。