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Intestinal inflammation targets cancer-inducing activity of the microbiota.

Science (New York, N.Y.) | Oct 5, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22903521

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.

Pubmed ID: 22903521 RIS Download

Mesh terms: Animals | Azoxymethane | Carcinogens | Carcinoma | Cell Transformation, Neoplastic | Colitis | Colorectal Neoplasms | DNA Damage | Escherichia coli | Interleukin-10 | Intestines | Metagenome | Mice | Mice, Mutant Strains | Polyketide Synthases | Sequence Deletion

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Associated grants

  • Agency: Canadian Institutes of Health Research, Id: MOP114872
  • Agency: NCI NIH HHS, Id: P30 CA016086
  • Agency: NIDDK NIH HHS, Id: P30 DK034987
  • Agency: PHS HHS, Id: P40 R018603
  • Agency: NCI NIH HHS, Id: R01 CA136887
  • Agency: NIDDK NIH HHS, Id: R01 DK047700
  • Agency: NIDDK NIH HHS, Id: R01 DK073338
  • Agency: NIDDK NIH HHS, Id: R01 DK47700
  • Agency: NIDDK NIH HHS, Id: R01 DK53347-11
  • Agency: NIDDK NIH HHS, Id: R01 DK73338
  • Agency: NIDDK NIH HHS, Id: T32 DK007737

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