Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice
Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice
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有机氯化物农药调节小鼠肠道微生物群并影响胆汁酸代谢。
DOI：
10.1016/j.envpol.2017.03.068
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发表时间：
2017-07-01
影响因子：
8.9
通讯作者：
Gu, Aihua
中科院分区：
文献类型：
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作者：
Liu, Qian;Shao, Wentao;Gu, Aihua
有机氯农药（OCPs）会在体内持续蓄积，威胁人类健康。胆汁酸和肠道微生物代谢已成为宿主体内重要的信号分子。然而，目前尚不清楚哪些肠道微生物群和胆汁酸会受到有机氯农药的影响。在本研究中，成年雄性C57BL/6小鼠连续8周暴露于对，对'-二氯二苯基二氯乙烯（p，p'-DDE）和β-六氯环己烷（β-HCH）中。通过16S rRNA基因测序分析各种细菌种类的相对丰度和组成。利用超高效液相色谱 - 质谱联用（UPLC-MS）的代谢组学分析方法来分析胆汁酸的组成。采用实时荧光定量聚合酶链反应（real-time PCR）检测肝脏和肠道中参与胆汁酸代谢的基因表达情况。在经p，p'-DDE和β-HCH孵育的HepG2细胞中检测胆汁酸合成与转运相关基因的表达。我们的研究结果表明，有机氯农药改变了肠道微生物群的相对丰度和组成，尤其是增强了具有胆盐水解酶（BSH）活性的乳杆菌。有机氯农药影响了胆汁酸的组成，增强了其疏水性，降低了回肠末端胆汁酸重吸收相关基因的表达，同时肝脏中胆汁酸合成相关基因的表达出现代偿性增加。我们证实，长期接触有机氯农药会损害肠道微生物群，进而影响肝脏和肠道的胆汁酸谱及代谢。本研究结果提醒我们，长期接触有机氯农药对胆汁酸代谢的调节存在危害，这可能会引发代谢紊乱，并有可能导致人类患上相关疾病。（C）2017爱思唯尔有限公司。保留所有权利。
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 8-hexachlorocyclohexane (beta-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 beta-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. (C) 2017 Elsevier Ltd. All rights reserved.