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| Status |
Public on Feb 12, 2014 |
| Title |
Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice [BeadArray] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The preferential localization of some neoplasms, such as serrated polyps, in specific areas of the intestine suggests that non-genetic 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 develop serrated polyps only in the cecum.
Here we show that a host-specific microbiome was associated with serrated polyps, and that alterations of the microbiota induced by antibiotic treatment or by embryo-transfer rederivation markedly inhibited the formation of serrated polyps in the cecum. Mechanistically, development of serrated polyps 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 number of neutrophils were found within the serrated polyps, and their depletion significantly reduced polyp growth.
Together these results indicate that non-genetic factors contribute to the development of serrated polyps 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.
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| Overall design |
Paired design; Surrounding and SP samples were obtained from the same mouse (n=3; mouse 1, 2, 3)
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| Contributor(s) |
Bongers G, Pacer ME, Geraldino TH, Chen L, He Z, Hashimoto D, Furtado GC, Ochando J, Kelley KA, Clemente JC, Merad M, van Bakel H, Lira SA |
| Citation(s) |
24590763 |
| Submission date |
Jun 07, 2013 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Gerold Bongers |
| E-mail(s) |
gerold.bongers@mssm.edu
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Immunology Institute
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| Street address |
1425 Madison Ave, 12-26A
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029-6574 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE47736 |
Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice |
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| Relations |
| BioProject |
PRJNA207542 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE47734_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE47734_non-normalized.txt.gz |
544.8 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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