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

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 to baseline temporal variation. We examined the distal gut microbiota of three individuals over 10 months that spanned two courses of the antibiotic ciprofloxacin, analyzing more than 1.7 million bacterial 16S rRNA hypervariable region sequences from 52-56 samples per subject. Inter-individual 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 days of drug initiation. By one week after the end of each course, communities began to return toward their initial state, but the return was often incomplete. While 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 regime with a stable average state. Antibiotic perturbation may cause a shift to an alternative stable state, the full consequences of which remain unknown.