Gut microbiome critically impacts PCB-induced changes in metabolic fingerprints and the hepatic transcriptome in mice

Polychlorinated biphenyls (PCBs) are ubiquitously detected in the environment and have been linked to metabolic diseases. The liver serves as a central hub for the metabolism of xenobiotics and endogenous metabolites. Gut dysbiosis is recognized as a critical regulator of disease susceptibility, however, little is known regarding how PCBs and gut microbiome interact to modulate the interface between xenobiotic and intermediary metabolism. We hypothesized that the gut microbiome regulates PCBs-mediated changes in the metabolic fingerprints and hepatic transcriptome. Ninety-day-old female conventional (CV) and germ-free (GF) C57BL/6 mice were orally exposed to the PCB Fox River Mixture (synthetic PCB mixture, 6 or 30 mg/kg) or corn oil (vehicle control, 10 ml/kg), once daily for 3 consecutive days. Organs were collected 24 hours after the final dose. RNA-Seq was conducted on liver, and endogenous aqueous metabolites (amino acids, carbohydrates, and nucleotides) were measured in liver and ...

多氯联苯（Polychlorinated biphenyls, PCBs）在环境中广泛检出，且与代谢性疾病存在关联。肝脏是外源性物质与内源性代谢物代谢的核心枢纽。肠道菌群失调被认定为疾病易感性的关键调控因子，然而目前对于多氯联苯与肠道微生物组如何交互调控外源性物质代谢与中间代谢之间的交互界面，仍知之甚少。我们提出假说：肠道微生物组可调控多氯联苯介导的代谢指纹图谱及肝脏转录组改变。本研究将90日龄雌性常规饲养（conventional, CV）与无菌（germ-free, GF）C57BL/6小鼠经口暴露于福克斯河多氯联苯混合物（合成多氯联苯混合物，剂量为6或30 mg/kg）或玉米油（溶剂对照，剂量为10 ml/kg），连续3天每日给药一次。末次给药后24小时采集脏器样本，对肝脏开展RNA测序，并检测肝脏及……中的内源性水溶性代谢物（氨基酸、碳水化合物与核苷酸）。