Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice.

ABSTRACT: 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 host-specific 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

SUBMITTER: Bongers G 

PROVIDER: S-EPMC3949565 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature