Intestinal Inflammation Targets Cancer-inducing Activity of the Microbiota

Overview

Journal Science

Specialty Science

Date 2012 Aug 21

PMID 22903521

Citations 1124

Authors

Janelle C Arthur

Ernesto Perez-Chanona

Marcus Muhlbauer

Sarah Tomkovich

Joshua M Uronis

Ting-Jia Fan

Barry J Campbell

Turki Abujamel

Belgin Dogan

Arlin B Rogers

Jonathan M Rhodes

Alain Stintzi

Kenneth W Simpson

Jonathan J Hansen

Temitope O Keku

Anthony A Fodor

Christian Jobin

Affiliations

Soon will be listed here.

Abstract

Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10-deficient (Il10(-/-)) mice. Monocolonization with the commensal Escherichia coli NC101 promoted invasive carcinoma in azoxymethane (AOM)-treated Il10(-/-) mice. Deletion of the polyketide synthase (pks) genotoxic island from E. coli NC101 decreased tumor multiplicity and invasion in AOM/Il10(-/-) mice, without altering intestinal inflammation. Mucosa-associated pks(+) E. coli were found in a significantly high percentage of inflammatory bowel disease and CRC patients. This suggests that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities.

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