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Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans
Carles Ubeda, Ying Taur, Robert R. Jenq, Michele J. Equinda, Tammy Son, Miriam Samstein, Agnes Viale, Nicholas D. Socci, Marcel R.M. van den Brink, Mini Kamboj, Eric G. Pamer
Carles Ubeda, Ying Taur, Robert R. Jenq, Michele J. Equinda, Tammy Son, Miriam Samstein, Agnes Viale, Nicholas D. Socci, Marcel R.M. van den Brink, Mini Kamboj, Eric G. Pamer
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Research Article

Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans

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Abstract

Bloodstream infection by highly antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), is a growing clinical problem that increasingly defies medical intervention. Identifying patients at high risk for bacterial sepsis remains an important clinical challenge. Recent studies have shown that antibiotics can alter microbial diversity in the intestine. Here, we characterized these effects using 16s rDNA pyrosequencing and demonstrated that antibiotic treatment of mice enabled exogenously administered VRE to efficiently and nearly completely displace the normal microbiota of the small and large intestine. In the clinical setting, we found that intestinal domination by VRE preceded bloodstream infection in patients undergoing allogeneic hematopoietic stem cell transplantation. Our results demonstrate that antibiotics perturb the normal commensal microbiota and set the stage for intestinal domination by bacteria associated with hospital-acquired infections. Thus, high-throughput DNA sequencing of the intestinal microbiota could identify patients at high risk of developing bacterial sepsis.

Authors

Carles Ubeda, Ying Taur, Robert R. Jenq, Michele J. Equinda, Tammy Son, Miriam Samstein, Agnes Viale, Nicholas D. Socci, Marcel R.M. van den Brink, Mini Kamboj, Eric G. Pamer

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Figure 6

Incomplete recovery of the microbiota after ampicillin treatment.

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Incomplete recovery of the microbiota after ampicillin treatment.
Four g...
Four groups of mice were treated with ampicillin and allowed to recover from ampicillin treatment. Each group of mice was housed in a separate cage. 1 mouse per cage was euthanized at weeks 1, 2, 4, or 8 after antibiotic withdrawal, and the ileum and cecum was harvested for microbiota analysis. As controls, 4 mice were euthanized before antibiotic treatment. (A) Unweighted UniFrac analysis of ileum or cecum samples. Each point represents the microbiota of an individual mouse. (B) Phylogenetic classification of 16S rDNA frequencies in the ileum and cecum. Each bar represents the microbiota of an individual mouse. The most predominant bacterial populations identified are color coded as indicated.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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