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Research Article

Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation

Les Dethlefsen and David A. Relman
  1. aDepartment of Microbiology and Immunology and Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305; and
  2. bVeterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304

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PNAS March 15, 2011 108 (Supplement 1) 4554-4561; first published September 16, 2010; https://doi.org/10.1073/pnas.1000087107
Les Dethlefsen
aDepartment of Microbiology and Immunology and Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305; and
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David A. Relman
aDepartment of Microbiology and Immunology and Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305; and
bVeterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304
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  • For correspondence: relman@stanford.edu
  1. Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved August 17, 2010 (received for review March 15, 2010)

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Abstract

The indigenous human microbiota is essential to the health of the host. Although the microbiota can be affected by many features of modern life, we know little about its responses to disturbance, especially repeated disturbances, and how these changes compare with baseline temporal variation. We examined the distal gut microbiota of three individuals over 10 mo that spanned two courses of the antibiotic ciprofloxacin, analyzing more than 1.7 million bacterial 16S rRNA hypervariable region sequences from 52 to 56 samples per subject. Interindividual variation was the major source of variability between samples. Day-to-day temporal variability was evident but constrained around an average community composition that was stable over several months in the absence of deliberate perturbation. The effect of ciprofloxacin on the gut microbiota was profound and rapid, with a loss of diversity and a shift in community composition occurring within 3–4 d of drug initiation. By 1 wk after the end of each course, communities began to return to their initial state, but the return was often incomplete. Although broadly similar, community changes after ciprofloxacin varied among subjects and between the two courses within subjects. In all subjects, the composition of the gut microbiota stabilized by the end of the experiment but was altered from its initial state. As with other ecosystems, the human distal gut microbiome at baseline is a dynamic regimen with a stable average state. Antibiotic perturbation may cause a shift to an alternative stable state, the full consequences of which remain unknown.

  • human microbiome
  • microbial community resilience
  • alternative stable state
  • ecosystem
  • ciprofloxacin

Footnotes

  • ↵1To whom correspondence should be addressed. E-mail: relman{at}stanford.edu.
  • Author contributions: L.D. and D.A.R. designed research; L.D. performed research; L.D. contributed new reagents/analytic tools; L.D. and D.A.R. analyzed data; and L.D. and D.A.R. wrote the paper.

  • The authors declare no conflict of interest.

  • This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Microbes and Health,” held November 2–3, 2009, at the Arnold and Mabel Beckman Center of the National Academies of Sciences and Engineering in Irvine, CA. The complete program and audio files of most presentations are available on the NAS Web site at http://www.nasonline.org/SACKLER_Microbes_and_Health.

  • This article is a PNAS Direct Submission.

  • Database deposition: The sequences reported in this paper have been deposited in the NCBI Short Read Archive database (accession no. SRA020961).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1000087107/-/DCSupplemental.

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Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation
Les Dethlefsen, David A. Relman
Proceedings of the National Academy of Sciences Mar 2011, 108 (Supplement 1) 4554-4561; DOI: 10.1073/pnas.1000087107

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Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation
Les Dethlefsen, David A. Relman
Proceedings of the National Academy of Sciences Mar 2011, 108 (Supplement 1) 4554-4561; DOI: 10.1073/pnas.1000087107
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