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.

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评估单剂量抗生素后体内代谢组和微生物组的变化

抗生素是现代医学的支柱，但当它们杀死目标病原体时，它们通常会影响共生微生物群。抗生素引起的微生物群失调是一个日益增长的研究重点和健康问题，通常通过分析粪便样本进行评估。然而，这样的分析并没有说明抗生素如何影响整个宿主的微生物组，或者这些变化随后如何改变宿主化学。在这项研究中，我们研究了两种常见抗生素（氨苄西林或万古霉素）的单一肠胃外剂量对来自 25 个国家的 77 个不同身体部位的小鼠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。不同的器官。广谱药物氨苄西林对下消化道（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，治疗后 1 天的影响最大，代谢物丰度的变化不仅限于肠道。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的增加和 α 多样性的丧失相关。此外，抗生素治疗后 1 天，小鼠下胃肠道中的小肽升高。虽然单次胃肠外剂量的抗生素并没有彻底改变微生物组，但是，在肠道内外都观察到了代谢组的变化。