Freeman Spogli Institute for International Studies Program on Energy and Sustainable Development Stanford University


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

Journal Article

Authors
Les Dethlefsen - Department of Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine
David Relman - Professor, Medicine - Infectious Diseases and Professor, Microbiology & Immunology at Stanford School of Medicine; CISAC Affiliated Faculty Member

Published by
PNAS, Vol. 107 no. 39
September 16, 2010


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.