4.6 Article

Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis

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MUCOSAL IMMUNOLOGY
卷 3, 期 2, 页码 148-158

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NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2009.132

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资金

  1. National Institutes of Health (NIH) [AI61570, AI074878, T32 AI060516, S10RR024525]
  2. Training in Immune System Development and Regulation [T32 AI05528]
  3. Burroughs Wellcome Fund
  4. Crohn's and Colitis Foundation of America's William and Shelby Modell Family Foundation Research
  5. University of Pennsylvania (University Research Foundation
  6. Veterinary Center for Infectious Diseases Pilot
  7. National Institute of Diabetes and Digestive Kidney Diseases center [DK50306]
  8. Pennsylvania Department of Health

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Despite widespread use of antibiotics, few studies have measured their effects on the burden or diversity of bacteria in the mammalian intestine. We developed an oral antibiotic treatment protocol and characterized its effects on murine intestinal bacterial communities and immune cell homeostasis. Antibiotic administration resulted in a 10-fold reduction in the amount of intestinal bacteria present and sequencing of 16S rDNA segments revealed significant temporal and spatial effects on luminal and mucosal-associated communities including reductions in luminal Firmicutes and mucosal-associated Lactobacillus species, and persistence of bacteria belonging to the Bacteroidetes and Proteobacteria phyla. Concurrently, antibiotic administration resulted in reduced RELM beta production, and reduced production of interferon-gamma and interleukin-17A by mucosal CD4(+) T lymphocytes. This comprehensive temporal and spatial metagenomic analyses will provide a resource and framework to test the influence of bacterial communities in murine models of human disease.

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