Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella

Fabian Rivera-Chávez, Lillian F. Zhang, Franziska Faber, Christopher A. Lopez, Mariana X. Byndloss, Erin E. Olsan, Gege Xu, Eric M. Velazquez, Carlito B Lebrilla, Sebastian E. Winter, Andreas J Baumler

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187 Scopus citations

Abstract

The mammalian intestine is host to a microbial community that prevents pathogen expansion through unknown mechanisms, while antibiotic treatment can increase susceptibility to enteric pathogens. Here we show that streptomycin treatment depleted commensal, butyrate-producing Clostridia from the mouse intestinal lumen, leading to decreased butyrate levels, increased epithelial oxygenation, and aerobic expansion of Salmonella enterica serovar Typhimurium. Epithelial hypoxia and Salmonella restriction could be restored by tributyrin treatment. Clostridia depletion and aerobic Salmonella expansion were also observed in the absence of streptomycin treatment in genetically resistant mice but proceeded with slower kinetics and required the presence of functional Salmonella type III secretion systems. The Salmonella cytochrome bd-II oxidase synergized with nitrate reductases to drive luminal expansion, and both were required for fecal-oral transmission. We conclude that Salmonella virulence factors and antibiotic treatment promote pathogen expansion through the same mechanism: depletion of butyrate-producing Clostridia to elevate epithelial oxygenation, allowing aerobic Salmonella growth.

Original languageEnglish (US)
Pages (from-to)443-454
Number of pages12
JournalCell Host and Microbe
Volume19
Issue number4
DOIs
StatePublished - Apr 13 2016

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ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Rivera-Chávez, F., Zhang, L. F., Faber, F., Lopez, C. A., Byndloss, M. X., Olsan, E. E., Xu, G., Velazquez, E. M., Lebrilla, C. B., Winter, S. E., & Baumler, A. J. (2016). Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella. Cell Host and Microbe, 19(4), 443-454. https://doi.org/10.1016/j.chom.2016.03.004