Nontargeted Urinary Metabolite Profiling of a Mouse Model of Crohn's Disease
Nontargeted Urinary Metabolite Profiling of a Mouse Model of Crohn's Disease
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DOI：
10.1021/pr800999t
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Rowan, Daryl D.
中科院分区：
文献类型：
--
作者：
Lin, Hui-Ming;Edmunds, Shelley J.;Rowan, Daryl D.
Crohn's disease is an inflammatory disorder of the bowel, believed to arise from the dysregulation of intestinal mucosal immunity. The interleukin-10-deficient (IL-10(-/-)) mouse, which develops intestinal inflammation in the presence of gut microflora, serves as a mouse model of Crohn's disease. Nontargeted urinary metabolite profiling was carried out to identify systemic metabolic changes associated with the development of intestinal inflammation caused by IL10-deficiency. Spot urine samples, collected from IL10(-/-) and wildtype mice at ages 5.5, 7, 8.5, and 10.5 weeks old were analyzed by gas chromatography-mass spectrometry (GCMS). The data were analyzed using XCMS software, multiple t tests, and ANOVA. Among the key metabolic differences detected were elevated urinary levels of xanthurenic acid and fucose in IL10(-/-) mice relative to wildtype, indicating upregulation of tryptophan catabolism and perturbed fucosylation in IL10(-/-) mice. Three short-chain dicarboxylic acid metabolites were decreased in urine of IL10(-/-) mice relative to wildtype, suggesting the downregulation of fatty acid oxidation in IL10(-/-) mice. These metabolic differences were reproducible in an independent set of mice. This study demonstrates that nontargeted GCMS metabolite profiling of IL10(-/-) mice can provide insights into the metabolic effects of IL10-deficiency and identify potential markers of intestinal inflammation.
