Exploring Organism-wide Changes in the Metabolome and Microbiome Following a Single Dose of Antibiotic

Antibiotics are a mainstay of modern medicine, but as they kill their target pathogen(s), they often damage 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, nor how such changes subsequently alter host chemistry. In this study, we investigated the acute (1 d post-administration), and delayed (6 d post-administration) effects of a single systemic 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 d post-treatment, 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 vs. control mice. Additionally, small peptides were elevated in the lower gastrointestinal tract of 1 d post-antibiotic treated mice. While a single dose of systemic antibiotic did not drastically damage the microbiome, changes in the metabolome were nevertheless observed both within and outside the gut. This study provides a framework for how whole-organism –omics approaches may be employed to understand the impact of antibiotics on the entire host.