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利用斑马鱼大规模定义生态失调的环境决定因素。

Defining the environmental determinants of dysbiosis at scale with zebrafish.

作者信息

Sharpton Thomas J, Alexiev Alexandra, Tanguay Robyn L

机构信息

Department of Microbiology, Oregon State University, Corvallis, OR.

Department of Statistics, Oregon State University, Corvallis, OR.

出版信息

Curr Opin Toxicol. 2023 Dec;36. doi: 10.1016/j.cotox.2023.100430. Epub 2023 Sep 16.

Abstract

The gut microbiome, critical to maintaining vertebrate homeostasis, is susceptible to a various exposures. In some cases, these exposures induce dysbiosis, wherein the microbiome changes into a state conducive to disease progression. To better prevent, manage, and treat health disorders, we need to define which exposures induce dysbiosis. Contemporary methods face challenges due to the immense diversity of the exposome and the restricted throughput of conventional experimental tools used for dysbiosis evaluation. We propose integrating high-throughput model systems as an augment to traditional techniques for rapid identification of dysbiosis-inducing agents. Although high-throughput screening tools revolutionized areas such as pharmacology and toxicology, their incorporation in gut microbiome research remains limited. One particularly powerful high-throughput model system is the zebrafish, which affords access to scalable experimentation involving a complex gut microbiome. Numerous studies have employed this model to identify potential dysbiosis triggers. However, its potential could be further harnessed via innovative study designs, such as evaluation of synergistic effects from combined exposures, expansions to the methodological toolkit to discern causal effects of microbiota, and efforts to assess and improve the translational relevance of the model. Ultimately, this burgeoning experimental resource can accelerate the discovery of agents that underlie dysbiotic disorders.

摘要

肠道微生物群对维持脊椎动物体内平衡至关重要,且易受多种暴露因素影响。在某些情况下,这些暴露会引发生态失调,即微生物群转变为有利于疾病进展的状态。为了更好地预防、管理和治疗健康紊乱,我们需要确定哪些暴露会导致生态失调。由于暴露组的巨大多样性以及用于生态失调评估的传统实验工具通量有限,当代方法面临挑战。我们建议整合高通量模型系统,作为传统技术的补充,以快速识别导致生态失调的因素。尽管高通量筛选工具给药理学和毒理学等领域带来了变革,但它们在肠道微生物群研究中的应用仍然有限。一种特别强大的高通量模型系统是斑马鱼,它能够进行涉及复杂肠道微生物群的可扩展实验。许多研究已采用该模型来识别潜在的生态失调触发因素。然而,通过创新的研究设计,如评估联合暴露的协同效应、扩展方法工具包以辨别微生物群的因果效应,以及努力评估和提高模型的转化相关性,其潜力可以得到进一步挖掘。最终,这种新兴的实验资源能够加速对导致生态失调疾病的因素的发现。

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