Linked Life Data

21596995

Source:http://linkedlifedata.com/resource/pubmed/id/21596995

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-7-28
pubmed:abstractText
Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met), and its increase in patients with IBD indicates a disruption of Met metabolism; however, the role of Hcys and Met metabolism in IBD is not well understood. We hypothesized that disrupted Met metabolism from a B-vitamin-deficient diet would exacerbate experimental colitis. Mice were fed a B(6)-B(12)-deficient or control diet for 2 wk and then treated with dextran sodium sulfate (DSS) to induce colitis. We monitored disease activity during DSS treatment and collected plasma and tissue for analysis of inflammatory tissue injury and Met metabolites. We also quantified Met cycle activity by measurements of in vivo Met kinetics using [1-(13)C-methyl-(2)H(3)]methionine infusion in similarly treated mice. Unexpectedly, we found that mice given the B-vitamin-deficient diet had improved clinical outcomes, including increased survival, weight maintenance, and reduced disease scores. We also found lower histological disease activity and proinflammatory gene expression (TNF-? and inducible nitric oxide synthase) in the colon in deficient-diet mice. Metabolomic analysis showed evidence that these effects were associated with deficient B(6), as markers of B(12) function were only mildly altered. In vivo methionine kinetics corroborated these results, showing that the deficient diet suppressed transsulfuration but increased remethylation. Our findings suggest that disrupted Met metabolism attributable to B(6) deficiency reduces the inflammatory response and disease activity in DSS-challenged mice. These results warrant further human clinical studies to determine whether B(6) deficiency and elevated Hcys in patients with IBD contribute to disease pathobiology.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1522-1547
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
301
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G249-59
pubmed:meshHeading
pubmed-meshheading:21596995-Analysis of Variance, pubmed-meshheading:21596995-Animals, pubmed-meshheading:21596995-Body Weight, pubmed-meshheading:21596995-Colitis, pubmed-meshheading:21596995-Dextran Sulfate, pubmed-meshheading:21596995-Gene Expression, pubmed-meshheading:21596995-Glutathione, pubmed-meshheading:21596995-Homocysteine, pubmed-meshheading:21596995-Inflammation, pubmed-meshheading:21596995-Interleukin-10, pubmed-meshheading:21596995-Kaplan-Meier Estimate, pubmed-meshheading:21596995-Male, pubmed-meshheading:21596995-Metabolomics, pubmed-meshheading:21596995-Methionine, pubmed-meshheading:21596995-Methylmalonic Acid, pubmed-meshheading:21596995-Mice, pubmed-meshheading:21596995-Mice, Inbred C57BL, pubmed-meshheading:21596995-Nitric Oxide Synthase Type II, pubmed-meshheading:21596995-Peroxidase, pubmed-meshheading:21596995-Pyridoxal Phosphate, pubmed-meshheading:21596995-S-Adenosylhomocysteine, pubmed-meshheading:21596995-Severity of Illness Index, pubmed-meshheading:21596995-Tumor Necrosis Factor-alpha, pubmed-meshheading:21596995-Vitamin B 12 Deficiency, pubmed-meshheading:21596995-Vitamin B 6 Deficiency
pubmed:year
2011
pubmed:articleTitle
B-vitamin deficiency is protective against DSS-induced colitis in mice.
pubmed:affiliation
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural