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Nat Commun. 2015 Jun 30;6:7486. doi: 10.1038/ncomms8486.

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.

Author information

1
Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
2
1] Department of Medicine, New York University School of Medicine, New York, New York 10016, USA [2] Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
3
1] Department of Medicine, New York University School of Medicine, New York, New York 10016, USA [2] New York Harbor Department of Veterans Affairs Medical Center, New York, New York 10010, USA.
4
The Genome Institute at Washington University, St. Louis, Missouri 63108, USA.
5
1] The Genome Institute at Washington University, St. Louis, Missouri 63108, USA [2] Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA, 63110 [3] The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06117, USA.
6
Division of Biostatistics, Department of Population Health, NYU Langone Medical Center, New York, New York 10016, USA.
7
1] The Genome Institute at Washington University, St. Louis, Missouri 63108, USA [2] Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
8
1] Department of Medicine, New York University School of Medicine, New York, New York 10016, USA [2] Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, New York 10016, USA.
9
1] The Genome Institute at Washington University, St. Louis, Missouri 63108, USA [2] The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06117, USA.
10
1] Department of Medicine, New York University School of Medicine, New York, New York 10016, USA [2] Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA [3] New York Harbor Department of Veterans Affairs Medical Center, New York, New York 10010, USA.

Abstract

Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

PMID:
26123276
PMCID:
PMC4491183
DOI:
10.1038/ncomms8486
[Indexed for MEDLINE]
Free PMC Article

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