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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. Supplement 1; pp. 4554 - 4561
• Main Authors: Dethlefsen, Les, Relman, David A
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15.03.2011; National Acad Sciences
• Series: Colloquium Paper
• Subjects: Antibiotics; Base Sequence; Biodiversity; Biological Sciences; Ciprofloxacin; Ciprofloxacin - pharmacology; Colloquium Papers; Colony Count, Microbial; Communities; Community composition; community structure; Datasets; Digestive tract; Drugs; Ecosystems; Feces - microbiology; Humans; intestinal microorganisms; Intestine, Large - microbiology; Metagenome - drug effects; Metagenome - genetics; Microbiota; Microorganisms; Molecular Sequence Data; Ordination; Phenotypic traits; Principal Component Analysis; ribosomal RNA; RNA, Ribosomal, 16S - genetics; rRNA 16S; Sequence Analysis, DNA; Taxa; temporal variation; Temporal variations; Time Factors
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1000087107

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.