Publication Date:
2012-08-21
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645302/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645302/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arthur, Janelle C -- Perez-Chanona, Ernesto -- Muhlbauer, Marcus -- Tomkovich, Sarah -- Uronis, Joshua M -- Fan, Ting-Jia -- Campbell, Barry J -- Abujamel, Turki -- Dogan, Belgin -- Rogers, Arlin B -- Rhodes, Jonathan M -- Stintzi, Alain -- Simpson, Kenneth W -- Hansen, Jonathan J -- Keku, Temitope O -- Fodor, Anthony A -- Jobin, Christian -- MOP114872/Canadian Institutes of Health Research/Canada -- P30 CA016086/CA/NCI NIH HHS/ -- P30 DK034987/DK/NIDDK NIH HHS/ -- P40 R018603/PHS HHS/ -- R01 CA136887/CA/NCI NIH HHS/ -- R01 DK047700/DK/NIDDK NIH HHS/ -- R01 DK073338/DK/NIDDK NIH HHS/ -- R01 DK47700/DK/NIDDK NIH HHS/ -- R01 DK53347-11/DK/NIDDK NIH HHS/ -- R01 DK73338/DK/NIDDK NIH HHS/ -- T32 DK007737/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):120-3. doi: 10.1126/science.1224820. Epub 2012 Aug 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22903521" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Azoxymethane/toxicity
;
Carcinogens/toxicity
;
Carcinoma/chemically induced/*microbiology/pathology
;
Cell Transformation, Neoplastic/genetics/pathology
;
Colitis/*complications/genetics
;
Colorectal Neoplasms/chemically induced/*microbiology/pathology
;
*DNA Damage
;
Escherichia coli/genetics/pathogenicity
;
Interleukin-10/genetics
;
Intestines/*microbiology/pathology
;
Metagenome/genetics/*physiology
;
Mice
;
Mice, Mutant Strains
;
Polyketide Synthases/genetics
;
Sequence Deletion
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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