Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks.
Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks.
复制标题
使用Transkingdom基因网络发现抗生素对宿主和微生物群的影响。
DOI：
10.1136/gutjnl-2014-308820
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发表时间：
2015-11
期刊：
影响因子：
24.5
通讯作者：
Shulzhenko N
中科院分区：
文献类型：
--
作者：
Morgun A;Dzutsev A;Dong X;Greer RL;Sexton DJ;Ravel J;Schuster M;Hsiao W;Matzinger P;Shulzhenko N
尽管抗生素被广泛用于治疗危及生命的感染和研究共生微生物群的作用，但我们对它们对宿主的影响的了解仍然非常有限。使用一种流行的抗生素鸡尾酒微生物群消耗小鼠模型，我们通过结合肠道转录组和肠道微生物群宏基因组分析来分析抗生素的影响。为了鉴定影响抗生素治疗小鼠宿主表型的特定微生物和微生物基因，我们开发并应用了跨王国网络分析。我们发现，大多数抗生素引起的肠道变化可以用三个因素来解释：微生物群的消耗；抗生素对宿主组织的直接影响和剩余耐药微生物的影响。正常微生物群的减少主要导致免疫各方面的下调。另外两个因素（抗生素对宿主组织的直接影响和抗生素耐药微生物）主要抑制线粒体基因表达和活性线粒体的数量，增加上皮细胞死亡。通过重建和分析跨王国网络，我们发现这些毒性作用是由抗生素耐药细菌的毒力/群体感应介导的，这一发现在体外实验中得到了进一步验证。除了揭示抗生素诱导改变的机制外，本研究还描述了一种新的生物信息学方法，该方法预测了调节宿主功能的微生物成分，并在广泛使用的抗生素微生物群消耗小鼠模型中建立了抗生素影响肠道的内容，原因和方式的综合资源。
Despite widespread use of antibiotics for the treatment of life-threatening infections and for research on the role of commensal microbiota, our understanding of their effects on the host is still very limited. Using a popular mouse model of microbiota depletion by a cocktail of antibiotics, we analysed the effects of antibiotics by combining intestinal transcriptome together with metagenomic analysis of the gut microbiota. In order to identify specific microbes and microbial genes that influence the host phenotype in antibiotic-treated mice, we developed and applied analysis of the transkingdom network. We found that most antibiotic-induced alterations in the gut can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues and the effects of remaining antibiotic-resistant microbes. Normal microbiota depletion mostly led to downregulation of different aspects of immunity. The two other factors (antibiotic direct effects on host tissues and antibiotic-resistant microbes) primarily inhibited mitochondrial gene expression and amounts of active mitochondria, increasing epithelial cell death. By reconstructing and analysing the transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria, a finding further validated using in vitro experiments. In addition to revealing mechanisms of antibiotic-induced alterations, this study also describes a new bioinformatics approach that predicts microbial components that regulate host functions and establishes a comprehensive resource on what, why and how antibiotics affect the gut in a widely used mouse model of microbiota depletion by antibiotics.
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影响因子：
64.8
作者：
Brandl, Katharina;Plitas, George;Mihu, Coralia N.;Ubeda, Carles;Jia, Ting;Fleisher, Martin;Schnabl, Bernd;DeMatteo, Ronald P.;Pamer, Eric G.
通讯作者：
Pamer, Eric G.
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
8
作者：
通讯作者：
--
DOI：
10.1038/nrmicro2259
发表时间：
2010-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Cox LM;Yamanishi S;Sohn J;Alekseyenko AV;Leung JM;Cho I;Kim SG;Li H;Gao Z;Mahana D;Zárate Rodriguez JG;Rogers AB;Robine N;Loke P;Blaser MJ
通讯作者：
Blaser MJ