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Recovery of the gut microbiota after antibiotics depends on host diet and environmental reservoirs

View ORCID ProfileKatharine M. Ng, View ORCID ProfileAndrés Aranda-Diaz, View ORCID ProfileCarolina Tropini, Matthew Ryan Frankel, William W. Van Treuren, Colleen O’Laughlin, View ORCID ProfileBryan D. Merrill, Feiqiao Brian Yu, Kali M. Pruss, View ORCID ProfileRita Almeida Oliveira, Steven K. Higginbottom, View ORCID ProfileNorma F. Neff, Michael A. Fischbach, View ORCID ProfileKarina B. Xavier, View ORCID ProfileJustin L. Sonnenburg, View ORCID ProfileKerwyn Casey Huang
doi: https://doi.org/10.1101/717686
Katharine M. Ng
1Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
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  • ORCID record for Katharine M. Ng
Andrés Aranda-Diaz
1Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
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  • ORCID record for Andrés Aranda-Diaz
Carolina Tropini
2Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
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  • ORCID record for Carolina Tropini
Matthew Ryan Frankel
1Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
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William W. Van Treuren
2Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
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Colleen O’Laughlin
1Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
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Bryan D. Merrill
2Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
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Feiqiao Brian Yu
3Chan Zuckerberg Biohub, San Francisco, CA 94158
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Kali M. Pruss
2Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
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Rita Almeida Oliveira
4Instituto Gulbenkian de Ciência, Oeiras, Portugal
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  • ORCID record for Rita Almeida Oliveira
Steven K. Higginbottom
2Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
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Norma F. Neff
3Chan Zuckerberg Biohub, San Francisco, CA 94158
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  • ORCID record for Norma F. Neff
Michael A. Fischbach
1Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
3Chan Zuckerberg Biohub, San Francisco, CA 94158
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Karina B. Xavier
4Instituto Gulbenkian de Ciência, Oeiras, Portugal
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Justin L. Sonnenburg
2Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
3Chan Zuckerberg Biohub, San Francisco, CA 94158
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Kerwyn Casey Huang
1Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
2Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
3Chan Zuckerberg Biohub, San Francisco, CA 94158
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  • ORCID record for Kerwyn Casey Huang
  • For correspondence: kchuang@stanford.edu
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Summary

That antibiotics alter microbiota composition and increase infection susceptibility is well known, but their generalizable effects on the gut commensal community and dependence on environmental variables remain open questions. Here, we systematically compared antibiotic responses in gnotobiotic and conventional mice across antibiotics, microbiotas, diets, and housing status. We identify remarkable resilience, whereby a humanized microbiota recovers before drug administration ends, with transient dominance of resistant Bacteroides and taxa-asymmetric reduction in diversity. In other cases, in vitro sensitivities were not predictive of in vivo responses, underscoring the significance of host and community contexts. A fiber-deficient diet exacerbated collapse of the microbiota and delayed recovery, despite the presence of a similar core community across diets at the point of maximal disturbance. Resilience to a second ciprofloxacin treatment was observed via response reprogramming, in which species replacement after ciprofloxacin treatment established resilience to a second treatment, and also through cross housing transmission. Single-housing drastically disrupted recovery, highlighting the importance of environmental microbial reservoirs and suggesting sanitation may exacerbate the duration of antibiotic-mediated disruption. Our findings highlight the ability of the commensal microbiota to deterministically adapt to large perturbations, and the translational potential for modulating diet, sanitation, and microbiota composition during antibiotics.

Footnotes

  • Lead author: Kerwyn Casey Huang (kchuang{at}stanford.edu)

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Recovery of the gut microbiota after antibiotics depends on host diet and environmental reservoirs
Katharine M. Ng, Andrés Aranda-Diaz, Carolina Tropini, Matthew Ryan Frankel, William W. Van Treuren, Colleen O’Laughlin, Bryan D. Merrill, Feiqiao Brian Yu, Kali M. Pruss, Rita Almeida Oliveira, Steven K. Higginbottom, Norma F. Neff, Michael A. Fischbach, Karina B. Xavier, Justin L. Sonnenburg, Kerwyn Casey Huang
bioRxiv 717686; doi: https://doi.org/10.1101/717686
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Recovery of the gut microbiota after antibiotics depends on host diet and environmental reservoirs
Katharine M. Ng, Andrés Aranda-Diaz, Carolina Tropini, Matthew Ryan Frankel, William W. Van Treuren, Colleen O’Laughlin, Bryan D. Merrill, Feiqiao Brian Yu, Kali M. Pruss, Rita Almeida Oliveira, Steven K. Higginbottom, Norma F. Neff, Michael A. Fischbach, Karina B. Xavier, Justin L. Sonnenburg, Kerwyn Casey Huang
bioRxiv 717686; doi: https://doi.org/10.1101/717686

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