Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 211, Issue 3, Pages 457-472Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20131587
Keywords
-
Categories
Funding
- G. Bongers
- CAPES Foundation (Brazil)
- National Institutes of Health grants [1R01CA161373- 01, P01 DK072201]
Ask authors/readers for more resources
The preferential localization of some neoplasms, such as serrated polyps (SPs), in specific areas of the intestine suggests that nongenetic factors may be important for their development. To test this hypothesis, we took advantage of transgenic mice that expressed HB- EGF throughout the intestine but developed SPs only in the cecum. Here we show that a hostspecific microbiome was associated with SPs and that alterations of the microbiota induced by antibiotic treatment or by embryo transfer rederivation markedly inhibited the formation of SPs in the cecum. Mechanistically, development of SPs was associated with a local decrease in epithelial barrier function, bacterial invasion, production of antimicrobials, and increased expression of several inflammatory factors such as IL-17, Cxcl2, Tnf-alpha, and IL-1. Increased numbers of neutrophils were found within the SPs, and their depletion significantly reduced polyp growth. Together these results indicate that nongenetic factors contribute to the development of SPs and suggest that the development of these intestinal neoplasms in the cecum is driven by the interplay between genetic changes in the host, an inflammatory response, and a host-specific microbiota.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available