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

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...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of experimental medicine Vol. 211; no. 3; pp. 457 - 472
Main Authors:	Bongers, Gerold, Pacer, Michelle E, Geraldino, Thais H, Chen, Lili, He, Zhengxiang, Hashimoto, Daigo, Furtado, Glaucia C, Ochando, Jordi, Kelley, Kevin A, Clemente, Jose C, Merad, Miriam, van Bakel, Harm, Lira, Sergio A
Format:	Journal Article
Language:	English
Published:	United States The Rockefeller University Press 10-03-2014
Subjects:	Animals Anti-Bacterial Agents - pharmacology Cecum - pathology Cytokines - metabolism Epithelium - physiology Gene Expression Regulation, Neoplastic - immunology Heparin-binding EGF-like Growth Factor Intercellular Signaling Peptides and Proteins - metabolism Intestinal Polyps - metabolism Intestinal Polyps - pathology Mice Mice, Transgenic Microbiota - physiology Models, Molecular Protein Conformation Species Specificity
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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-α, 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1007 1540-9538
DOI:	10.1084/jem.20131587