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Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll‐like receptor 2‐knockout mice
Author(s) -
Kellermayer Richard,
Dowd Scot E.,
Harris R. Alan,
Balasa Alfred,
Schaible Tiffany D.,
Wolcott Randy D.,
Tatevian Nina,
Szigeti Reka,
Li Zhijie,
Versalovic James,
Smith C. Wayne
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-172205
Subject(s) - biology , microbiome , epigenomics , tlr2 , dna methylation , immune system , transcriptome , pattern recognition receptor , innate immune system , gut flora , toll like receptor , microbiology and biotechnology , immunology , gene , genetics , gene expression
The connection between intestinal micro‐biota and host physiology is increasingly becoming recognized. The details of this dynamic interaction, however, remain to be explored. Toll‐like receptor 2 (Tlr2) is important for its role in bacterial recognition, intestinal inflammation, and obesity‐related metabolic changes. Therefore, we sought to determine the epigenomic and metagenomic consequences of Tlr2 deficiency in the colonic mucosa of mice to gain insights into biological pathways that shape the interface between the gut micro‐biota and the mammalian host. Colonic mucosa from wild type (WT) and Tlr2 −/− C57BL/6 mice was interrogated by microarrays specific for DNA methylation and gene expression. The mucosal microbiome was studied by next‐generation pyrosequencing of bacterial 16S rRNA The expression of genes involved in immune processes was significantly modified by the absence of Tlr2 , a number of which correlated with DNA methylation changes. The epigenomic and transcriptomic modifications associated with alteration in mucosal microbial composition. Several bacterial species, including members of the Firmicutes were significantly different in abundance between WT and Tlr2 −/− animals. This manuscript highlights the intimate interrelationships between expression of immune‐related genes and immunity pathways in the host with compositional and functional differences of the mammalian microbiome.—Kellermayer, R., Dowd, S. E., Harris, R. A., Balasa, A., Schaible, T. D., Wolcott, R. D., Tatevian, N., Szigeti, R., Li, Z., Versalovic, J., Smith, C. W. Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll‐like receptor 2‐knockout mice. FASEB J. 25, 1449–1460 (2011). www.fasebj.org