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一种定量方法来测量和预测微生物组对抗生素的反应。

A quantitative approach to measure and predict microbiome response to antibiotics.

机构信息

Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

出版信息

mSphere. 2024 Sep 25;9(9):e0048824. doi: 10.1128/msphere.00488-24. Epub 2024 Sep 4.

Abstract

UNLABELLED

Although antibiotics induce sizable perturbations in the human microbiome, we lack a systematic and quantitative method to measure and predict the microbiome's response to specific antibiotics. Here, we introduce such a method, which takes the form of a microbiome response index (MiRIx) for each antibiotic. Antibiotic-specific MiRIx values quantify the overall susceptibility of the microbiota to an antibiotic, based on databases of bacterial phenotypes and published data on intrinsic antibiotic susceptibility. We applied our approach to five published microbiome studies that carried out antibiotic interventions with vancomycin, metronidazole, ciprofloxacin, amoxicillin, and doxycycline. We show how MiRIx can be used in conjunction with existing microbiome analytical approaches to gain a deeper understanding of the microbiome response to antibiotics. Finally, we generate antibiotic response predictions for the oral, skin, and gut microbiome in healthy humans. Our approach is implemented as open-source software and is readily applied to microbiome data sets generated by 16S rRNA marker gene sequencing or shotgun metagenomics.

IMPORTANCE

Antibiotics are potent influencers of the human microbiome and can be a source for enduring dysbiosis and antibiotic resistance in healthcare. Existing microbiome data analysis methods can quantify perturbations of bacterial communities but cannot evaluate whether the differences are aligned with the expected activity of a specific antibiotic. Here, we present a novel method to quantify and predict antibiotic-specific microbiome changes, implemented in a ready-to-use software package. This has the potential to be a critical tool to broaden our understanding of the relationship between the microbiome and antibiotics.

摘要

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尽管抗生素会对人体微生物组产生相当大的干扰,但我们缺乏一种系统的、定量的方法来测量和预测微生物组对特定抗生素的反应。在这里,我们引入了这样一种方法,它采用了每种抗生素的微生物组反应指数(MiRIx)的形式。基于细菌表型数据库和已发表的关于固有抗生素敏感性的数据,抗生素特异性 MiRIx 值定量了微生物组对抗生素的整体敏感性。我们将我们的方法应用于五项已发表的微生物组研究,这些研究对万古霉素、甲硝唑、环丙沙星、阿莫西林和强力霉素进行了抗生素干预。我们展示了如何结合现有的微生物组分析方法,使用 MiRIx 来更深入地了解抗生素对微生物组的反应。最后,我们为健康人类的口腔、皮肤和肠道微生物组生成抗生素反应预测。我们的方法以开源软件的形式实现,并可轻松应用于通过 16S rRNA 标记基因测序或鸟枪法宏基因组学生成的微生物组数据集。

重要性

抗生素是人体微生物组的有力影响因素,并且可能是医疗保健中持久的菌群失调和抗生素耐药性的来源。现有的微生物组数据分析方法可以量化细菌群落的扰动,但不能评估这些差异是否与特定抗生素的预期活性一致。在这里,我们提出了一种新的方法来量化和预测抗生素特异性微生物组变化,该方法以即用型软件包实现。这有可能成为拓宽我们对微生物组和抗生素之间关系的理解的关键工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34c7/11423569/f1efcac8baf5/msphere.00488-24.f001.jpg

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