Gut Microbiota Modulates Interactions Between Polychlorinated Biphenyls and Bile Acid Homeostasis
Gut Microbiota Modulates Interactions Between Polychlorinated Biphenyls and Bile Acid Homeostasis
复制标题
DOI：
10.1093/toxsci/kfy208
复制
发表时间：
2018-12-01
影响因子：
3.8
通讯作者：
Cui, Julia Yue
中科院分区：
文献类型：
--
作者：
Cheng, Sunny Lihua;Li, Xueshu;Cui, Julia Yue
肠道微生物组越来越被认为是有助于宿主健康和疾病的第二个基因组。肠道微生物群的主要功能是将肝脏中胆固醇产生的初级胆汁酸（BA）转化为次级BA，其激活不同的宿主受体以调节异生物质代谢和能量稳态。本研究的目的是调查在何种程度上口腔暴露于环境相关的多氯联苯（多氯联苯混合物），即福克斯河混合物，影响肠道微生物组和BA稳态。将90日龄成年雌性常规（CV）和无菌（GF）C57 BL/6小鼠经口暴露于玉米油（溶剂）或Fox River混合物，剂量为6或30 mg/kg，每日一次，连续3天。低剂量PCB显著增加BA代谢相关细菌Akkermansia（A.）muciniphila、梭菌Clostridium（C.）在CV小鼠的大肠颗粒（LIP）中的肠球菌属、肠球菌属和肠球菌属（16 S rRNA测序/qPCR）。这与PCB低剂量介导的血清和小肠内容物（SIP）中多种BA以肠道微生物群依赖性方式（UPLC-MS/MS）增加有关。相反，在PCB高剂量下，CV小鼠中BA水平保持稳定，与肝外排转运蛋白和回肠Fgf 15的增加相关。有趣的是，肠道微生物群的缺乏增强了肝脏、SIP和LIP中牛磺酸缀合的α和β鼠胆酸的PCB介导的增加。Pearson相关分析表明，5个类群与大多数二级BA之间存在正相关关系。总之，多氯联苯剂量依赖性地改变BA的稳态，通过共同努力之间的主机肠-肝轴和肠道细菌。
The gut microbiome is increasingly recognized as a second genome that contributes to the health and diseases of the host. A major function of the gut microbiota is to convert primary bile acids (BAs) produced from cholesterol in the liver into secondary BAs that activate distinct host receptors to modulate xenobiotic metabolism and energy homeostasis. The goal of this study was to investigate to what extent oral exposure to an environmentally relevant polychlorinated biphenyl (PCBs mixture), namely the Fox River mixture, impacts gut microbiome and BA homeostasis. Ninety-day-old adult female conventional (CV) and germ-free (GF) C57BL/6 mice were orally exposed to corn oil (vehicle), or the Fox River mixture at 6 or 30 mg/kg once daily for 3 consecutive days. The PCB low dose profoundly increased BA metabolism related bacteria Akkermansia (A.) muciniphila, Clostridium (C.) scindens, and Enterococcus in the large intestinal pellet (LIP) of CV mice (16S rRNA sequencing/qPCR). This correlated with a PCB low dose-mediated increase in multiple BAs in serum and small intestinal content (SIP) in a gut microbiota-dependent manner (UPLC-MS/MS). Conversely, at PCB high dose, BA levels remained stable in CV mice correlated with an increase in hepatic efflux transporters and ileal Fgf15. Interestingly, lack of gut microbiota potentiated the PCB-mediated increase in taurine conjugated alpha and beta muricholic acids in liver, SIP, and LIP. Pearson's correlation identified positive correlations between 5 taxa and most secondary BAs. In conclusion, PCBs dose-dependently altered BA homeostasis through a joint effort between host gut-liver axis and intestinal bacteria.