| Maternal methyl-donor supplementation induces prolonged murine offspring colitis susceptibility in association with mucosal epigenetic and microbiomic changes. | |
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MedLine Citation:
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PMID: 21296867 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Developmental epigenetic changes, such as DNA methylation, have been recognized as potential pathogenic factors in inflammatory bowel diseases, the hallmark of which is an exaggerated immune response against luminal microbes. A methyl-donor (MD) diet can modify DNA methylation at select murine genomic loci during early development. The components of the MDs are routinely incorporated into prenatal human supplements. Therefore, we studied the effects of maternal MD supplementation on offspring colitis susceptibility and colonic mucosal DNA methylation and gene expression changes in mice as a model. Additionally, we investigated the offspring mucosal microbiomic response to the maternal dietary supplementation. Colitis was induced by dextran sulfate sodium. Colonic mucosa from offspring of MD-supplemented mothers following reversal to control diet at weaning was interrogated by methylation-specific microarrays and pyrosequencing at postnatal days 30 (P30) and P90. Transcriptomic changes were analyzed by microarray profiling and real-time reverse transcription polymerase chain reaction. The mucosal microbiome was studied by high throughput pyrosequencing of 16S rRNA. Maternal MD supplementation induced a striking susceptibility to colitis in offspring. This phenotype was associated with colonic mucosal DNA methylation and expression changes. Metagenomic analyses did not reveal consistent bacteriomic differences between P30 and P90, but showed a prolonged effect of the diet on the offspring mucosal microbiome. In conclusion, maternal MD supplementation increases offspring colitis susceptibility that associates with persistent epigenetic and prolonged microbiomic changes. These findings underscore that epigenomic reprogramming relevant to mammalian colitis can occur during early development in response to maternal dietary modifications. |
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Authors:
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Tiffany D Schaible; R Alan Harris; Scot E Dowd; C Wayne Smith; Richard Kellermayer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2011-02-04 |
Journal Detail:
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Title: Human molecular genetics Volume: 20 ISSN: 1460-2083 ISO Abbreviation: Hum. Mol. Genet. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-07 Completed Date: 2011-08-15 Revised Date: 2012-05-01 |
Medline Journal Info:
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Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: England |
Other Details:
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Languages: eng Pagination: 1687-96 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, USDA/ARS Children's Nutrition Research Center, Houston, TX, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bacteria / classification, genetics, isolation & purification Betaine / administration & dosage, adverse effects Choline / administration & dosage, adverse effects Colitis / etiology, genetics, metabolism*, microbiology DNA Methylation Dietary Supplements / adverse effects* Disease Susceptibility* / metabolism Epigenesis, Genetic* Female Folic Acid / administration & dosage, adverse effects Humans Intestinal Mucosa / metabolism, microbiology* Male Maternal Nutritional Physiological Phenomena* Metagenome* Mice Mice, Inbred C57BL Pedigree Pregnancy Prenatal Exposure Delayed Effects / genetics, metabolism*, microbiology Vitamin B 12 / administration & dosage, adverse effects |
| Grant Support | |
ID/Acronym/Agency:
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U54HG004592/HG/NHGRI NIH HHS |
| Chemical | |
Reg. No./Substance:
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107-43-7/Betaine; 59-30-3/Folic Acid; 62-49-7/Choline; 68-19-9/Vitamin B 12 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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