Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic

ABSTRACT 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...

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Autores principales:	Alison Vrbanac, Kathryn A. Patras, Alan K. Jarmusch, Robert H. Mills, Samuel R. Shing, Robert A. Quinn, Fernando Vargas, David J. Gonzalez, Pieter C. Dorrestein, Rob Knight, Victor Nizet
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	3D data visualization antibiotics mass spectrometry metabolome microbiome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/94d799acd998420094b81a585a2e6543
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spelling	oai:doaj.org-article:94d799acd998420094b81a585a2e65432021-12-02T19:46:19ZEvaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic10.1128/mSystems.00340-202379-5077https://doaj.org/article/94d799acd998420094b81a585a2e65432020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00340-20https://doaj.org/toc/2379-5077ABSTRACT 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.Alison VrbanacKathryn A. PatrasAlan K. JarmuschRobert H. MillsSamuel R. ShingRobert A. QuinnFernando VargasDavid J. GonzalezPieter C. DorresteinRob KnightVictor NizetAmerican Society for Microbiologyarticle3D data visualizationantibioticsmass spectrometrymetabolomemicrobiomeMicrobiologyQR1-502ENmSystems, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	3D data visualization antibiotics mass spectrometry metabolome microbiome Microbiology QR1-502
spellingShingle	3D data visualization antibiotics mass spectrometry metabolome microbiome Microbiology QR1-502 Alison Vrbanac Kathryn A. Patras Alan K. Jarmusch Robert H. Mills Samuel R. Shing Robert A. Quinn Fernando Vargas David J. Gonzalez Pieter C. Dorrestein Rob Knight Victor Nizet Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic
description	ABSTRACT 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.
format	article
author	Alison Vrbanac Kathryn A. Patras Alan K. Jarmusch Robert H. Mills Samuel R. Shing Robert A. Quinn Fernando Vargas David J. Gonzalez Pieter C. Dorrestein Rob Knight Victor Nizet
author_facet	Alison Vrbanac Kathryn A. Patras Alan K. Jarmusch Robert H. Mills Samuel R. Shing Robert A. Quinn Fernando Vargas David J. Gonzalez Pieter C. Dorrestein Rob Knight Victor Nizet
author_sort	Alison Vrbanac
title	Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic
title_short	Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic
title_full	Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic
title_fullStr	Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic
title_full_unstemmed	Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic
title_sort	evaluating organism-wide changes in the metabolome and microbiome following a single dose of antibiotic
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/94d799acd998420094b81a585a2e6543
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Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic

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