Journal
MBIO
Volume 10, Issue 5, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/mBio.02244-19
Keywords
Escherichia coli; colibactin; colorectal cancer; microbiome
Categories
Funding
- USDA/NIFA [2015-67015-22930]
- Public Health Service [AI044170, AI096528, AI112445, AI112949]
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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 colibactinproducing 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-nducing activity of the microbiota.
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