Intestinal inflammation targets cancer-inducing activity of the microbiota.
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.
Department of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Janelle C
JC
Arthur
Ernesto
E
Perez-Chanona
Marcus
M
Mühlbauer
Sarah
S
Tomkovich
Joshua M
JM
Uronis
Ting-Jia
TJ
Fan
Barry J
BJ
Campbell
Turki
T
Abujamel
Belgin
B
Dogan
Arlin B
AB
Rogers
Jonathan M
JM
Rhodes
Alain
A
Stintzi
Kenneth W
KW
Simpson
Jonathan J
JJ
Hansen
Temitope O
TO
Keku
Anthony A
AA
Fodor
Christian
C
Jobin
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002277:Carcinoma / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D003092:Colitis / Q000150:complications* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology; D004249:DNA Damage; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity; D016753:Interleukin-10 / Q000235:genetics; D007422:Intestines / Q000382:microbiology* / Q000473:pathology; D054892:Metagenome / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D048630:Polyketide Synthases / Q000235:genetics; D017384:Sequence Deletion
D002273:Carcinogens; D016753:Interleukin-10; D048630:Polyketide Synthases; D001397:Azoxymethane