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Recovery of the Gut Microbiota after Antibiotics Depends on Host Diet and Environmental Reservoirs

72 Pages Posted: 31 Jan 2019 Sneak Peek Status: Review Complete

See all articles by Katharine M. Ng

Katharine M. Ng

Stanford University - Department of Bioengineering

Andrés Aranda-Diaz

Stanford University - Department of Bioengineering

Carolina Tropini

Stanford University, School of Medicine, Department of Microbiology and Immunology

Matthew Ryan Frankel

Stanford University - Department of Bioengineering

William W. Van Treuren

Stanford University - Department of Microbiology and Immunology

Colleen O’Laughlin

Stanford University - Department of Bioengineering

Bryan D. Merrill

Stanford University - Department of Microbiology and Immunology

Feiqiao Brian Yu

Chan Zuckerberg Biohub

Kali M. Pruss

Stanford University - Department of Microbiology and Immunology

Rita Almeida Oliveira

Instituto Gulbenkian de Ciência

Steven K. Higginbottom

Stanford University - Department of Microbiology and Immunology

Norma Neff

Chan Zuckerberg Biohub

Michael Fischbach

Stanford University - Department of Bioengineering; Chan Zuckerberg Biohub

Karina B. Xavier

Instituto Gulbenkian de Ciência

Justin L. Sonnenburg

Stanford University - Department of Microbiology and Immunology; Chan Zuckerberg Biohub

Kerwyn Casey Huang

Stanford University - Biophysics Graduate Program; Chan Zuckerberg Biohub

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Abstract

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 oligodominance and taxa-asymmetric reduction in diversity. In general, in vitro sensitivities were not predictive of in vivo responses, underscoring the significance of community context. A fiber-deficient diet exacerbated collapse of the microbiota. We also observed response reprogramming, in which species replacement after ciprofloxacin treatment established resilience to a second treatment, as did transmission through cross-housing. Single-housing drastically disrupted recovery, highlighting the importance of sanitation and environmental reservoirs. 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. 

Keywords: gut microbiota, antibiotics, resilience, reseeding, co-housing, coprophagia, microbiota perturbations

Suggested Citation

Ng, Katharine M. and Aranda-Diaz, Andrés and Tropini, Carolina and Frankel, Matthew Ryan and Van Treuren, William W. and O’Laughlin, Colleen and Merrill, Bryan D. and Yu, Feiqiao Brian and Pruss, Kali M. and Oliveira, Rita Almeida and Higginbottom, Steven K. and Neff, Norma and Fischbach, Michael and Xavier, Karina B. and Sonnenburg, Justin L. and Huang, Kerwyn Casey, Recovery of the Gut Microbiota after Antibiotics Depends on Host Diet and Environmental Reservoirs (January 29, 2019). Available at SSRN: https://ssrn.com/abstract=3325029 or http://dx.doi.org/10.2139/ssrn.3325029
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Katharine M. Ng

Stanford University - Department of Bioengineering

Stanford, CA 94305
United States

Andrés Aranda-Diaz

Stanford University - Department of Bioengineering

Stanford, CA 94305
United States

Carolina Tropini

Stanford University, School of Medicine, Department of Microbiology and Immunology

Stanford, CA 94305
United States

Matthew Ryan Frankel

Stanford University - Department of Bioengineering

Stanford, CA 94305
United States

William W. Van Treuren

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Colleen O’Laughlin

Stanford University - Department of Bioengineering

Stanford, CA 94305
United States

Bryan D. Merrill

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Feiqiao Brian Yu

Chan Zuckerberg Biohub

499 Illinois Street
San Francisco, CA 94158
United States

Kali M. Pruss

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Rita Almeida Oliveira

Instituto Gulbenkian de Ciência

Oeiras
Portugal

Steven K. Higginbottom

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Norma Neff

Chan Zuckerberg Biohub

499 Illinois Street
San Francisco, CA 94158
United States

Michael Fischbach

Stanford University - Department of Bioengineering

Stanford, CA 94305
United States

Chan Zuckerberg Biohub

499 Illinois Street
San Francisco, CA 94158
United States

Karina B. Xavier

Instituto Gulbenkian de Ciência

Oeiras
Portugal

Justin L. Sonnenburg

Stanford University - Department of Microbiology and Immunology

Stanford, CA 94305
United States

Chan Zuckerberg Biohub

499 Illinois Street
San Francisco, CA 94158
United States

Kerwyn Casey Huang (Contact Author)

Stanford University - Biophysics Graduate Program ( email )

Stanford, CA 94305
United States

Chan Zuckerberg Biohub ( email )

499 Illinois Street
San Francisco, CA 94158
United States

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