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

Connections (1)

This publication is referenced by other Labnodes entities: