Increased Epithelial Oxygenation Links Colitis to an Expansion of Tumorigenic Bacteria.

Cevallos SA, Lee JY, Tiffany CR, Byndloss AJ, Johnston L, Byndloss MX, Bäumler AJ
mBio. 2019 10 (5)

PMID: 31575772 · PMCID: PMC6775460 · DOI:10.1128/mBio.02244-19

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 within the gut-associated microbial community through aerobic respiration. An aerobic expansion of colibactin-producing 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. 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 , 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.

Copyright © 2019 Cevallos et al.

MeSH Terms (15)

Aerobiosis Animals Carcinogenesis Colitis Colorectal Neoplasms Dextran Sulfate Escherichia coli Escherichia coli Infections Female Gastrointestinal Microbiome Mice Mice, Inbred C57BL Oxygen Peptides Polyketides

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