[Show abstract][Hide abstract] ABSTRACT: The interleukin-10-deficient (IL-10(-/-)) mouse, a model of inflammatory bowel disease (IBD), develops intestinal inflammation unless raised in germ-free conditions. The metabolic effects of consuming extracts from the fruits of yellow (Actinidia chinensis) or green-fleshed (A. deliciosa) kiwifruit that displayed in vitro anti-inflammatory activity were investigated in IL-10(-/-) mice by metabolomic analysis of urine samples. Kiwifruit-derived metabolites were detected at significantly higher levels in urine of IL-10(-/-) mice relative to those of wild-type mice, indicating that the metabolism of these metabolites was affected by IL-10(-/-)-wild-type genotypic differences. Urinary metabolites previously associated with inflammation were not altered by the kiwifruit extracts. This study demonstrates the use of metabolomic analysis to study dietary effects and the influence of genotype on food metabolism, which may have implications on the development of functional foods for the treatment of IBD.
[Show abstract][Hide abstract] ABSTRACT: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) attributed to a dysregulated immune response towards intestinal microbiota. Although various susceptibility genes have been identified for CD and UC, the exact disease etiology is unclear and complicated by the influence of environmental factors. Metabolomic analysis enables high sample throughput measurements of multiple metabolites in biological samples. The use of metabolomic analysis in medical sciences has revealed metabolite perturbations associated with diseases. This article provides a summary of the current understanding of IBD, and describes potential applications and previous metabolomic analysis in IBD research to understand IBD pathogenesis and improve IBD therapy.
[Show abstract][Hide abstract] ABSTRACT: The interleukin-10-deficient (IL10(-/-)) mouse develops colon inflammation in response to normal intestinal microflora and has been used as a model of Crohn's disease. Short-Column LCMS metabolite profiling of urine from IL10(-/-) and wild-type (WT) mice was used, in two independent experiments, to identify mass spectral ions differing in intensity between these two genotypes. Three differential metabolites were identified as xanthurenic acid and as the glucuronides of xanthurenic acid and of α-CEHC (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman). The significance of several differential metabolites as potential biomarkers of colon inflammation was evaluated in an experiment which compared metabolite concentrations in IL10(-/-) and WT mice housed, either under conventional conditions and dosed with intestinal microflora, or maintained under specific pathogen-free (SPF) conditions. Concentrations of xanthurenic acid, α-CEHC glucuronide, and an unidentified metabolite m/z 495(-)/497(+) were associated with the degree of inflammation in IL10(-/-) mice and may prove useful as biomarkers of colon inflammation.
BioMed Research International 01/2011; 2011:974701. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interleukin-10 is an immunosuppressive cytokine involved in the regulation of gastrointestinal mucosal immunity toward intestinal microbiota. Interleukin-10-deficient (IL10(-/-)) mice develop Crohn's disease-like colitis unless raised in germ-free conditions. Previous gas chromatography-mass spectrometry (GC-MS) metabolomic analysis revealed urinary metabolite differences between IL10(-/-) and wildtype C57BL/6 mice. To determine which of these differences were specifically associated with intestinal inflammation arising from IL10-deficiency, urine samples from IL10(-/-) and wildtype mice, housed in either conventional or specific pathogen-free conditions, were subjected to GC-MS metabolomic analysis. Fifteen metabolite differences, including fucose, xanthurenic acid, and 5-aminovaleric acid, were associated with intestinal inflammation. Elevated urinary levels of xanthurenic acid in IL10(-/-) mice were attributed to increased production of kynurenine metabolites that may induce T-cell tolerance toward intestinal microbiota. Liquid chromatography-mass spectrometry analysis confirmed that plasma levels of kynurenine and 3-hydroxykynurenine were elevated in IL10(-/-) mice. Eleven metabolite differences, including glutaric acid, 2-hydroxyglutaric acid, and 2-hydroxyadipic acid, were unaffected by the severity of inflammation. These metabolite differences may be associated with residual genes from the embryonic stem cells of the 129P2 mouse strain that were used to create the IL10(-/-) mouse, or may indicate novel functions of IL10 unrelated to inflammation.
Journal of Proteome Research 02/2010; 9(4):1965-75. · 5.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Crohn's disease is an inflammatory disorder of the bowel, believed to arise from the dysregulation of intestinal mucosal immunity. The interleukin-10-deficient (IL10-/-) 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.
Journal of Proteome Research 05/2009; 8(4):2045-57. · 5.00 Impact Factor