Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic.
Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic.
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DOI：
10.1128/msystems.00340-20
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发表时间：
2020-10-06
期刊：
影响因子：
6.4
通讯作者：
Nizet V
中科院分区：
文献类型：
--
作者：
Vrbanac A;Patras KA;Jarmusch AK;Mills RH;Shing SR;Quinn RA;Vargas F;Gonzalez DJ;Dorrestein PC;Knight R;Nizet V
我们刚刚开始了解抗生素对我们的微生物组和健康的意外影响。在这项研究中，我们的目的是定义一种方法，通过这种方法可以获得（i）抗生素如何时空影响整个肠道的肠道微生物，以及（ii）这些变化如何影响整个身体的宿主化学。我们发现，仅仅一剂抗生素就改变了各种器官中的宿主化学，并且整个肠道的微生物组变化并不均匀。随着技术进步增加了全生物体研究的可行性，我们认为使用这些方法可以进一步了解抗生素对健康的广泛影响以及如何恢复微生物群落以减轻这些影响。抗生素是现代医学的支柱，但当它们杀死目标病原体时，它们通常会影响肠道微生物群。抗生素诱导的微生物群生态失调是一个日益增长的研究焦点和健康问题，通常通过分析粪便样本进行评估。然而，这种分析并没有告知抗生素如何影响整个宿主的微生物组，或者这些变化如何随后改变宿主的化学性质。在这项研究中，我们研究了两种常见抗生素氨苄青霉素或万古霉素单次胃肠外给药对小鼠25个不同器官77个不同身体部位的整体代谢组和微生物组的急性（给药后1天）和延迟（给药后6天）影响。广谱药物氨苄青霉素对下胃肠道（盲肠和结肠）的微生物群影响最大，那里的微生物多样性最高。在代谢组中，给药后1天观察到最大影响，代谢物丰度的变化不限于肠道。与对照小鼠相比，氨苄青霉素及其代谢物的局部丰度与代谢组效应大小增加和α多样性丧失相关。此外，抗生素治疗后1天，小鼠下胃肠道中的小肽升高。虽然单次注射抗生素并没有显著改变微生物组，但在肠道内外都观察到了代谢组的变化。这项研究提供了一个框架，如何整体生物体组学方法可以用来了解抗生素对整个主机的影响。我们才刚刚开始了解抗生素对我们的微生物组和健康的意外影响。在这项研究中，我们的目的是定义一种方法，通过这种方法可以获得（i）抗生素如何时空影响整个肠道的肠道微生物，以及（ii）这些变化如何影响整个身体的宿主化学。我们发现，仅仅一剂抗生素就改变了各种器官中的宿主化学，并且整个肠道的微生物组变化并不均匀。随着技术进步增加了全生物体研究的可行性，我们认为使用这些方法可以进一步了解抗生素对健康的广泛影响以及如何恢复微生物群落以减轻这些影响。
We are just beginning to understand the unintended effects of antibiotics on our microbiomes and health. In this study, we aimed to define an approach by which one could obtain a comprehensive picture of (i) how antibiotics spatiotemporally impact commensal microbes throughout the gut and (ii) how these changes influence host chemistry throughout the body. We found that just a single dose of antibiotic altered host chemistry in a variety of organs and that microbiome alterations were not uniform throughout the gut. As technological advances increase the feasibility of whole-organism studies, we argue that using these approaches can provide further insight on both the wide-ranging effects of antibiotics on health and how to restore microbial communities to mitigate these effects. Antibiotics are a mainstay of modern medicine, but as they kill their target pathogen(s), they often affect the commensal microbiota. Antibiotic-induced microbiome dysbiosis is a growing research focus and health concern, often assessed via analysis of fecal samples. However, such analysis does not inform how antibiotics influence the microbiome across the whole host or how such changes subsequently alter host chemistry. In this study, we investigated the acute (1 day postadministration) and delayed (6 days postadministration) effects of a single parenteral dose of two common antibiotics, ampicillin or vancomycin, on the global metabolome and microbiome of mice across 77 different body sites from 25 different organs. The broader-spectrum agent ampicillin had the greatest impact on the microbiota in the lower gastrointestinal tract (cecum and colon), where microbial diversity is highest. In the metabolome, the greatest effects were seen 1 day posttreatment, and changes in metabolite abundances were not confined to the gut. The local abundance of ampicillin and its metabolites correlated with increased metabolome effect size and a loss of alpha diversity versus control mice. Additionally, small peptides were elevated in the lower gastrointestinal tract of mice 1 day after antibiotic treatment. While a single parenteral dose of antibiotic did not drastically alter the microbiome, nevertheless, changes in the metabolome were observed both within and outside the gut. This study provides a framework for how whole-organism -omics approaches can be employed to understand the impact of antibiotics on the entire host. IMPORTANCE We are just beginning to understand the unintended effects of antibiotics on our microbiomes and health. In this study, we aimed to define an approach by which one could obtain a comprehensive picture of (i) how antibiotics spatiotemporally impact commensal microbes throughout the gut and (ii) how these changes influence host chemistry throughout the body. We found that just a single dose of antibiotic altered host chemistry in a variety of organs and that microbiome alterations were not uniform throughout the gut. As technological advances increase the feasibility of whole-organism studies, we argue that using these approaches can provide further insight on both the wide-ranging effects of antibiotics on health and how to restore microbial communities to mitigate these effects.