Nontargeted urinary metabolite profiling of a mouse model of Crohn's disease.
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.
Lin
Hui-Ming
HM
School of Medical Sciences, University of Auckland, Auckland, New Zealand.
Edmunds
Shelley I
SI
Helsby
Nuala A
NA
Ferguson
Lynnette R
LR
Rowan
Daryl D
DD
D000818:Animals; D003424:Crohn Disease / Q000378:metabolism* / Q000652:urine; D004195:Disease Models, Animal; D018928:Immunity, Mucosal; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D014556:Urine / Q000737:chemistry*
D016753:Interleukin-10