Abstract:
:The microbiota is pivotal in the pathogenesis of inflammatory bowel disease (IBD)-associated inflammation-induced colorectal cancer (CRC), yet mechanisms for these effects remain poorly characterized. Here, we demonstrate that aberrant inflammasome-induced microbiota plays a critical role in CRC development, where mice deficient in the NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome feature enhanced inflammation-induced CRC formation. Intriguingly, WT mice cohoused either with inflammasome-deficient mice or with mice lacking IL-18 feature exacerbated inflammation-induced CRC compared with singly housed WT mice. Enhanced tumorigenesis is dependent on microbiota-induced chemokine (C-C motif) ligand 5 (CCL5)-driven inflammation, which in turn promotes epithelial cell proliferation through local activation of the IL-6 pathway, leading to cancer formation. Altogether, our results mechanistically link the altered microbiota with the pathogenesis of inflammation-induced CRC and suggest that in some conditions, microbiota components may transfer CRC susceptibility between individuals.
journal_name
Proc Natl Acad Sci U S Aauthors
Hu B,Elinav E,Huber S,Strowig T,Hao L,Hafemann A,Jin C,Wunderlich C,Wunderlich T,Eisenbarth SC,Flavell RAdoi
10.1073/pnas.1307575110subject
Has Abstractpub_date
2013-06-11 00:00:00pages
9862-7issue
24eissn
0027-8424issn
1091-6490pii
1307575110journal_volume
110pub_type
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