Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of American Society for Microbiology for personal use, not for redistribution. The definitive version was published in Infection and Immunity 77 (2009): 2367-2375, doi:10.1128/IAI.01520-08.Shifts in microbial communities are implicated in the pathogenesis of a number of gastrointestinal diseases, but we have limited understanding of the mechanisms that lead to altered community structures. One difficulty with studying these mechanisms in human subjects is the inherent baseline variability of the microbiota in different individuals that arise due to varying life histories. To try and overcome this baseline variability we employed a mouse model to control host genotype, diet and other possible influences on the microbiota. This allowed us to determine if the indigenous microbiota in such mice had a stable baseline community structure and whether this community exhibited a consistent response following antibiotic administration. We employed a tag sequencing strategy targeting the V6 hypervariable region of the bacterial small-subunit (16S) ribosomal RNA combined with massively parallel sequencing to determine the community structure of the gut microbiota. Inbred mice in a controlled environment harbored a reproducible baseline community that was significantly impacted by antibiotic administration. The ability of the gut microbial community to recover to baseline following cessation of antibiotic administration varied according to the antibiotic regimen administered. Severe antibiotic pressure resulted in reproducible long-lasting alterations in the gut microbial community including a decrease in overall diversity. The finding of stereotypic responses of the indigenous microbiota to ecologic stress implies that a better understanding of the factors that govern community structure could lead to strategies for the intentional manipulation of this ecosystem to preserve or restore a healthy microbiota.The main projects were funded in whole with federal funds from the NIAID, NIH, Department of Health and Human Services, under contract number N01-AI-30058. Additional funding was supplied via subcontracts from the Woods Hole Center for Oceans and Human Health from the National Institutes of Health and National Science Foundation (NIH/NIEHS 1 P50 ES012742-01 and NSF/OCE 0430724-J. Stegeman PI to H.G.M. and M.L.S. and R01 DK070875 to V.B.Y.) and a grants from the W.M. Keck Foundation and the G. Unger Vetlesen Foundation (to M.L.S.). D.A.A. was supported by the National Institutes of Health under a Ruth L. Kirschstein National Research Service Award (T32 HL07749)