title: Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice.
abstract: 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.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-2399, USA. kellerma@bcm.edu
authors.forename: Richard
authors.initials: R
authors.lastname: Kellermayer
authors.forename: Scot E
authors.initials: SE
authors.lastname: Dowd
authors.forename: R Alan
authors.initials: RA
authors.lastname: Harris
authors.forename: Alfred
authors.initials: A
authors.lastname: Balasa
authors.forename: Tiffany D
authors.initials: TD
authors.lastname: Schaible
authors.forename: Randy D
authors.initials: RD
authors.lastname: Wolcott
authors.forename: Nina
authors.initials: N
authors.lastname: Tatevian
authors.forename: Reka
authors.initials: R
authors.lastname: Szigeti
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Li
authors.forename: James
authors.initials: J
authors.lastname: Versalovic
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D003106:Colon / Q000378:metabolism*; D019295:Computational Biology; D019175:DNA Methylation / Q000235:genetics; D057890:Epigenomics; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012336:RNA, Ribosomal, 16S; D051195:Toll-Like Receptor 2