Organophosphate Diazinon Altered Quorum Sensing, Cell Motility, Stress Response, and Carbohydrate Metabolism of Gut Microbiome

Organophosphate Diazinon Altered Quorum Sensing, Cell Motility, Stress Response, and Carbohydrate Metabolism of Gut Microbiome
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DOI:
10.1093/toxsci/kfx053
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发表时间:
2017-06-01
影响因子:
3.8
通讯作者:
Lu, Kun
Lu, Kun
中科院分区:
医学2区
文献类型:
--
作者:
Gao, Bei;Bian, Xiaoming;Lu, Kun

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肠道微生物群在能量生产、免疫系统发育和宿主抵抗入侵病原体等方面起着关键作用。肠道细菌动态平衡的破坏与许多人类疾病有关。据报道,几种环境化学物质可以引起肠道微生物群的改变。二氮磷是一种重要的有机磷杀虫剂,在农业上有着广泛的应用。二氮磷及其代谢物很容易在不同的环境和人体尿液中被检测到。有机磷的毒性一直是公共卫生关注的问题。我们最近证实,有机磷杀虫剂二氮磷扰乱了小鼠肠道微生物群的组成。然而,暴露对肠道微生物组的功能影响还没有得到充分的评估。特别是,导致暴露诱导的微生物谱和群落结构变化的分子机制尚未确定。因此,在这项研究中,我们使用元转录组学来研究二氮磷暴露对C57BL/6小鼠肠道代谢组的影响。在这里,我们首次证明了有机磷二氮磷对群体感应的调节,这可能是调节细菌种群、组成,更重要的是调节其功能基因的关键机制。此外,我们还发现,二氮磷暴露激活了多种应激反应途径,并严重损害了肠道细菌的能量代谢。这些发现为肠道微生物群与环境化学物质(如有机磷)之间的功能相互作用提供了新的理解。
The gut microbiome plays a key role in energy production, immune system development, and host resistance against invading pathogens, etc. Disruption of gut bacterial homeostasis is associated with a number of human diseases. Several environmental chemicals have been reported to induce alterations of the gut microbiome. Diazinon, one of important organophosphate insecticides, has been widely used in agriculture. Diazinon and its metabolites are readily detected in different environmental settings and human urine. The toxicity of organophosphates has been a long-standing public health concern. We recently demonstrated that organophosphate insecticide diazinon perturbed the gut microbiome composition of mice. However, the functional impact of exposure on the gut microbiome has not been adequately assessed yet. In particular, the molecular mechanism responsible for exposure-induced microbial profile and community structure changes has not been identified. Therefore, in this study, we used metatranscriptomics to examine the effects of diazinon exposure on the gut metatranscriptome in C57BL/6 mice. Herein, we demonstrated for the first time that organophosphate diazinon modulated quorum sensing, which may serve as a key mechanism to regulate bacterial population, composition, and more importantly, their functional genes. In addition, we also found that diazinon exposure activated diverse stress response pathways and profoundly impaired energy metabolism of gut bacteria. These findings provide new understandings of the functional interplay between the gut microbiome and environmental chemicals, such as organophosphates.