A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity

Victoria E. Ruiz, Thomas Battaglia, Zachary D. Kurtz, Luc Bijnens, Amy Ou, Isak Engstrand, Xuhui Zheng, Tadasu Iizumi, Briana J. Mullins, Christian L. Müller, Ken Cadwell, Richard Bonneau, Guillermo I. Perez-Perez and Martin J. Blaser ()
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Victoria E. Ruiz: New York University School of Medicine (NYUSM)
Thomas Battaglia: New York University School of Medicine (NYUSM)
Zachary D. Kurtz: New York University School of Medicine (NYUSM)
Luc Bijnens: Janssen R&D, Janssen Pharmaceutical Companies of J&J
Amy Ou: New York University School of Medicine (NYUSM)
Isak Engstrand: Karolinska Institutet
Xuhui Zheng: New York University School of Medicine (NYUSM)
Tadasu Iizumi: New York University School of Medicine (NYUSM)
Briana J. Mullins: New York University School of Medicine (NYUSM)
Christian L. Müller: Center for Computational Biology, Flatiron Institute, Simons Foundation
Ken Cadwell: Kimmel Center for Biology and Medicine at the Skirball Institute, NYUSM
Richard Bonneau: Center for Computational Biology, Flatiron Institute, Simons Foundation
Guillermo I. Perez-Perez: New York University School of Medicine (NYUSM)
Martin J. Blaser: New York University School of Medicine (NYUSM)

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Broad-spectrum antibiotics are frequently prescribed to children. Early childhood represents a dynamic period for the intestinal microbial ecosystem, which is readily shaped by environmental cues; antibiotic-induced disruption of this sensitive community may have long-lasting host consequences. Here we demonstrate that a single pulsed macrolide antibiotic treatment (PAT) course early in life is sufficient to lead to durable alterations to the murine intestinal microbiota, ileal gene expression, specific intestinal T-cell populations, and secretory IgA expression. A PAT-perturbed microbial community is necessary for host effects and sufficient to transfer delayed secretory IgA expression. Additionally, early-life antibiotic exposure has lasting and transferable effects on microbial community network topology. Our results indicate that a single early-life macrolide course can alter the microbiota and modulate host immune phenotypes that persist long after exposure has ceased.

Date: 2017
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DOI: 10.1038/s41467-017-00531-6

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