期刊
FASEB JOURNAL
卷 25, 期 5, 页码 1449-1460出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.10-172205
关键词
metagenomics; inflammatory bowel diseases; metabolic syndrome; epigenetics; Tlr2
资金
- Crohn's and Colitis Foundation of America-Children's Digestive Health and Nutrition Foundation/North American Society of Pediatric Gastroenterology Hepatology and Nutrition [CCFA 2426]
- Broad Medical Research Program
- Broad Foundation [IBD-0252]
- U.S. Department of Agriculture/Agriculture Research Service Child Health Research Center [6250-51000-055]
- National Human Genome Research Initiative ENCODE [U54HG004592]
- National Institute of Diabetes, Digestive, and Kidney Disease [R01 DK065075, UH3 DK083990, P30 DK56338]
- National Center for Complementary and Alternative Medicine [R01 AT004326]
The connection between intestinal microbiota 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 microbiota 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
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