Increased Epithelial Oxygenation Links Colitis to an Expansion of Tumorigenic Bacteria.
mBio
; 10(5)2019 10 01.
Article
em En
| MEDLINE
| ID: mdl-31575772
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Neoplasias Colorretais
/
Colite
/
Infecções por Escherichia coli
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Carcinogênese
/
Microbioma Gastrointestinal
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
MBio
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos