Increased Epithelial Oxygenation Links Colitis to an Expansion of Tumorigenic Bacteria

Stephanie A. Cevallos, Jee Yon Lee, Connor R. Tiffany, Austin J. Byndloss, Luana Johnston, Mariana X. Byndloss, Andreas J. Bäumler

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Intestinal inflammation is a risk factor for colorectal cancer formation, but the underlying mechanisms remain unknown. Here, we investigated whether colitis alters the colonic microbiota to enhance its cancer-inducing activity. Colitis increased epithelial oxygenation in the colon of mice and drove an expansion of Escherichia coli within the gut-associated microbial community through aerobic respiration. An aerobic expansion of colibactin-producing E. coli was required for the cancer-inducing activity of this pathobiont in a mouse model of colitis-associated colorectal cancer formation. We conclude that increased epithelial oxygenation in the colon is associated with an expansion of a prooncogenic driver species, thereby increasing the cancer-inducing activity of the microbiota.IMPORTANCE One of the environmental factors important for colorectal cancer formation is the gut microbiota, but the habitat filters that control its cancer-inducing activity remain unknown. Here, we show that chemically induced colitis elevates epithelial oxygenation in the colon, thereby driving an expansion of colibactin-producing Escherichia coli, a prooncogenic driver species. These data suggest that elevated epithelial oxygenation is a potential risk factor for colorectal cancer formation because the consequent changes in the gut habitat escalate the cancer-inducing activity of the microbiota.

Original languageEnglish (US)
JournalmBio
Volume10
Issue number5
DOIs
StatePublished - Oct 1 2019

Keywords

  • colibactin
  • colorectal cancer
  • Escherichia coli
  • microbiome

ASJC Scopus subject areas

  • Microbiology
  • Virology

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  • Cite this

    Cevallos, S. A., Lee, J. Y., Tiffany, C. R., Byndloss, A. J., Johnston, L., Byndloss, M. X., & Bäumler, A. J. (2019). Increased Epithelial Oxygenation Links Colitis to an Expansion of Tumorigenic Bacteria. mBio, 10(5). https://doi.org/10.1128/mBio.02244-19