title: Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.
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.
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Yael R
authors.initials: YR
authors.lastname: Nobel
authors.affiliation: 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.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Cox
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Francis F
authors.initials: FF
authors.lastname: Kirigin
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Bokulich
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamanishi
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Teitler
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Jiho
authors.initials: J
authors.lastname: Sohn
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Cecily M
authors.initials: CM
authors.lastname: Barber
authors.affiliation: 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.
authors.forename: David S
authors.initials: DS
authors.lastname: Goldfarb
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Kartik
authors.initials: K
authors.lastname: Raju
authors.affiliation: The Genome Institute at Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Sahar
authors.initials: S
authors.lastname: Abubucker
authors.affiliation: 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.
authors.forename: Yanjiao
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Ruiz
authors.affiliation: Division of Biostatistics, Department of Population Health, NYU Langone Medical Center, New York, New York 10016, USA.
authors.forename: Huilin
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Makedonka
authors.initials: M
authors.lastname: Mitreva
authors.affiliation: 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.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Alekseyenko
authors.affiliation: 1] The Genome Institute at Washington University, St. Louis, Missouri 63108, USA [2] The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06117, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Weinstock
authors.affiliation: 1] The Genome Institute at Washington University, St. Louis, Missouri 63108, USA [2] The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06117, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Sodergren
authors.affiliation: 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.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Blaser
mesh_terms: D000375:Aging; D000658:Amoxicillin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004734:Energy Metabolism / Q000502:physiology; D005243:Feces / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D056186:Metagenomics; D051379:Mice; D008810:Mice, Inbred C57BL; D059467:Transcriptome; D015645:Tylosin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000658:Amoxicillin; D015645:Tylosin