Genomics

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Comparison of murine colonic mucosal gene expression between offspring born to mothers fed a methyl donor diet (MD) versus control at postnatal day 90 (P90).


ABSTRACT: BACKGROUND & AIMS: Inflammatory Bowel Diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic illnesses that are thought to develop secondary to a pathologic interaction between the immune system and the intestinal microflora that is manifested by the gut mucosa. IBD has been recognized as disorders in which developmental epigenetic changes, such as DNA methylation, may play an important pathogenic role. DNA methylation can be influenced in mammals by dietary exposures. A methyl-donor diet has been specifically found to be effective in inducing permanent changes in DNA methylation at certain genomic loci in murine models. Importantly, the methyl-donor substances utilized are routinely incorporated into prenatal micronutrient supplements for humans. In this study we addressed whether maternal exposure to a methyl-donor diet induces prolonged alterations in offspring colitis susceptibility and whether it leads to stable colonic mucosal epigenetic changes and gene expression alterations in mice. We also assessed whether the maternal methyl-donor diet induced persistent changes in the colonic microbiota in the offspring. METHODS: Colonic mucosa from offspring of mothers fed a methyl donor diet (MD) or control diet was interrogated by methylation specific amplification microarray (MSAM) at postnatal day 30 (P30) and P90 to screen for changes in DNA methylation, with bisulfite pyrosequencing validation. Transcriptomic changes in the same tissue were analyzed by microarray expression profiling and real time RT-PCR. The mucosal microbiome was studied by high throughput, detailed pyrosequencing of 16S rRNA. RESULTS: MD exposure during prenatal and early development lead to a significant increase in colitis susceptibility that persisted even after 69 days of diet reversal (P90). MD exposure also influenced DNA methylation and expression at select genomic loci. Overlap between DNA methylation and gene expression changes was confirmed at Ppara, a gene previously implicated in murine colitis. Metagenomic analyses failed to reveal consistent bacteriomic differences between the P30 and P90 age groups. CONCLUSIONS: Prenatal and early developmental exposure to MD induces increased colitis susceptibility, mucosal epigenomic, and transcriptomic changes that do not appear to associate with consistent microbiomic alterations. These findings underscore the importance of maternal nutrition on offspring colitis susceptibility in mammals and implicate the importance of the associated mucosal epigenetic modification. Our results bare potentially significant public health relevance as well.

ORGANISM(S): Mus musculus

PROVIDER: GSE24354 | GEO | 2010/10/20

SECONDARY ACCESSION(S): PRJNA132807

REPOSITORIES: GEO

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