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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-10-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSystems.00340-20 |
| _version_ | 1818722244904353792 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T20:51:33Z |
| format | Article |
| id | doaj.art-94d799acd998420094b81a585a2e6543 |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-12-17T20:51:33Z |
| publishDate | 2020-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-94d799acd998420094b81a585a2e65432022-12-21T21:33:01ZengAmerican Society for MicrobiologymSystems2379-50772020-10-015510.1128/mSystems.00340-20Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of AntibioticAlison Vrbanac0Kathryn A. Patras1Alan K. Jarmusch2Robert H. Mills3Samuel R. Shing4Robert A. Quinn5Fernando Vargas6David J. Gonzalez7Pieter C. Dorrestein8Rob Knight9Victor Nizet10Department of Pediatrics, UC San Diego, La Jolla, California, USADepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USASkaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California, USADepartment of Pediatrics, UC San Diego, La Jolla, California, USADepartment of Pediatrics, UC San Diego, La Jolla, California, USADepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USASkaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California, USASkaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California, USADepartment of Pediatrics, UC San Diego, La Jolla, California, USADepartment of Pediatrics, UC San Diego, La Jolla, California, USADepartment of Pediatrics, UC San Diego, La Jolla, California, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mSystems.00340-203D data visualizationantibioticsmass spectrometrymetabolomemicrobiome |
| spellingShingle | 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 mSystems 3D data visualization antibiotics mass spectrometry metabolome microbiome |
| title | 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_short | 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 |
| topic | 3D data visualization antibiotics mass spectrometry metabolome microbiome |
| url | https://journals.asm.org/doi/10.1128/mSystems.00340-20 |
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