Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota
Year: 2012
Type: article
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.
Source: Science
Authors: Janelle C. Arthur, Ernesto Perez-Chanona, Marcus Mühlbauer, 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
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: North Carolina State University, Crohn's and Colitis Foundation, North West Cancer Research, National Institutes of Health, U.S. Public Health Service, Weill Cornell Medical College, Canadian Institutes of Health Research, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill
Awards: G1530900700, G1948135505, Intestinal Microbiota, Diet and Risk of Colorectal Adenomas, Regulation of immunosuppressive molecules in IBD, Role of Bacteria in Colitis-Associated Colon Cancer, G6192087833, G6552149642, G6569852626, Colitis Induced by immune responses to luminal bacteria-mouse, G9000271500, Center for Gastrointestinal Biology and Disease, Gastroenterology Research Training, Cancer Center Support Grant
OpenAlex ID: W2089643849