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阿特拉津暴露诱导的宿主-微生物组整合反应介导果蝇的毒性。

An integrated host-microbiome response to atrazine exposure mediates toxicity in Drosophila.

机构信息

Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.

Centre for Computational Biology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

出版信息

Commun Biol. 2021 Nov 24;4(1):1324. doi: 10.1038/s42003-021-02847-y.

Abstract

The gut microbiome produces vitamins, nutrients, and neurotransmitters, and helps to modulate the host immune system-and also plays a major role in the metabolism of many exogenous compounds, including drugs and chemical toxicants. However, the extent to which specific microbial species or communities modulate hazard upon exposure to chemicals remains largely opaque. Focusing on the effects of collateral dietary exposure to the widely used herbicide atrazine, we applied integrated omics and phenotypic screening to assess the role of the gut microbiome in modulating host resilience in Drosophila melanogaster. Transcriptional and metabolic responses to these compounds are sex-specific and depend strongly on the presence of the commensal microbiome. Sequencing the genomes of all abundant microbes in the fly gut revealed an enzymatic pathway responsible for atrazine detoxification unique to Acetobacter tropicalis. We find that Acetobacter tropicalis alone, in gnotobiotic animals, is sufficient to rescue increased atrazine toxicity to wild-type, conventionally reared levels. This work points toward the derivation of biotic strategies to improve host resilience to environmental chemical exposures, and illustrates the power of integrative omics to identify pathways responsible for adverse health outcomes.

摘要

肠道微生物组产生维生素、营养物质和神经递质,有助于调节宿主的免疫系统,同时在许多外源性化合物(包括药物和化学毒物)的代谢中也起着主要作用。然而,特定微生物种类或群落在接触化学物质时调节危害的程度在很大程度上仍不清楚。本研究聚焦于广泛使用的除草剂莠去津的偶然饮食暴露的影响,应用整合组学和表型筛选来评估肠道微生物组在调节黑腹果蝇宿主抗性中的作用。这些化合物的转录和代谢反应具有性别特异性,并强烈依赖于共生微生物组的存在。对果蝇肠道中所有丰富微生物的基因组进行测序,揭示了一种独特的负责莠去津解毒的酶途径,该途径仅存在于热带醋杆菌中。我们发现,在无菌动物中,仅热带醋杆菌就足以将野生型、常规饲养的动物对莠去津的毒性增加恢复到正常水平。这项工作指出了衍生生物策略以提高宿主对环境化学暴露的抗性,并说明了整合组学识别导致不良健康结果的途径的强大功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da29/8613235/1d910c1fdae9/42003_2021_2847_Fig1_HTML.jpg

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