Center of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of Medicine, Shanghai, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Environ Pollut. 2017 Jul;226:268-276. doi: 10.1016/j.envpol.2017.03.068. Epub 2017 Apr 6.
Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p'-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human.
有机氯农药(OCPs)会在体内持续积累,威胁人类健康。胆酸和肠道微生物代谢已成为宿主中的重要信号分子。然而,关于 OCPs 改变了哪些肠道微生物和胆酸,目前还不清楚。在这项研究中,成年雄性 C57BL/6 小鼠暴露于 p,p'-二氯二苯二氯乙烯(p,p'-DDE)和β-六氯环己烷(β-HCH)中 8 周。通过 16S rRNA 基因测序分析各种细菌物种的相对丰度和组成。通过 UPLC-MS 代谢组学分析分析胆酸组成。实时 PCR 测量与 p,p'-DDE 和 β-HCH 孵育的 HepG2 细胞中参与肝内和肠内胆酸代谢的基因表达。我们的研究结果表明,OCPs 改变了肠道微生物的相对丰度和组成,特别是增强了具有胆盐水解酶(BSH)活性的乳杆菌。OCPs 影响胆酸组成,增加疏水性,降低末端回肠中胆酸重吸收的基因表达,并代偿性增加肝脏中胆酸合成的基因表达。我们证明了 OCPs 的慢性暴露会损害肠道微生物群;因此,肝内和肠内胆酸谱和代谢受到影响。本研究的结果引起了我们对慢性 OCPs 暴露在调节胆酸代谢方面的危害的关注,这可能导致代谢紊乱,并有可能在人类中引起相关疾病。