[Report] Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota

1. Janelle C. Arthur¹,
2. Ernesto Perez-Chanona¹,
3. Marcus M?hlbauer¹,
4. Sarah Tomkovich¹,
5. Joshua M. Uronis¹,
6. Ting-Jia Fan¹,
7. Barry J. Campbell²,
8. Turki Abujamel³,⁴,
9. Belgin Dogan⁵,
10. Arlin B. Rogers⁶,
11. Jonathan M. Rhodes²,
12. Alain Stintzi³,
13. Kenneth W. Simpson⁵,
14. Jonathan J. Hansen¹,
15. Temitope O. Keku¹,
16. Anthony A. Fodor⁷,
17. Christian Jobin¹,*

1. ¹Department of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill, NC, USA.
2. ²Department of Gastroenterology, University of Liverpool, Liverpool, United Kingdom.
3. ³Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
4. ⁴Department of Medical Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
5. ⁵Clinical Sciences, Cornell University, Ithaca, NY, USA.
6. ⁶Lineberger Comprehensive Cancer Center, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA.
7. ⁷Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, NC, USA.

1. ?*To whom correspondence should be sent. E-mail: job{at}med.unc.edu

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 impacts 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.

• Received for publication 17 May 2012.
• Accepted for publication 1 August 2012.

Source: http://www.sciencemag.org/lookup/doi/10.1126/science.1224820?rss=1

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