Urinary NMR metabolomic profiles discriminate inflammatory bowel disease from healthy.

BACKGROUND AND AIMS: Inflammatory bowel disease, a chronic inflammation of the intestinal tract, presents in two variations, Ulcerative Colitis (UC) and Crohn's disease (CD). Given that treatment of CD differs from UC, a single test that provided strong diagnostic ability would offer great clinical value. Two previous studies have indicated that CD can be distinguished from UC, and that both can be distinguished from non-IBD-type gastrointestinal disease, based on urinary and faecal metabolite profiling. METHODS: Analysis of healthy as well as CD and UC patients attending an IBD clinic was performed. IBD patients were classified into two groups (CD or UC) based on chart review of clinical, endoscopic, and histological assessment. Urine samples were obtained and analyzed using nuclear magnetic resonance (NMR) spectroscopy combined with targeted profiling techniques, followed by univariate and multivariate statistical analysis. RESULTS: Based on urinary metabolomics, individuals with IBD could be differentiated from healthy. Major differences between IBD and healthy included TCA cycle intermediates, amino acids, and gut microflora metabolites. Comparison of CD and UC patients revealed discrimination, but removal of patients with the surgical intervention confounder revealed that CD could not be discriminated from UC. CONCLUSIONS: This study highlights the potential for metabolomics to distinguish IBD from the healthy state but shows that careful consideration must be given to establishing disease-representative cohorts that are free of confounding factors.

Dextran sulfate sodium inhibits alanine synthesis in Caco-2 cells.

To understand and characterize the pathogenic mechanisms of inflammatory bowel disease, dextran sulfate sodium (DSS) has been used to induce acute and chronic colitis in animal models by causing intestinal epithelium damage. The mechanism of action of DSS in producing this outcome is not well understood. In an effort to understand how DSS might impact epithelial cell metabolism, we studied the intestinal epithelial cell line Caco-2 incubated with 1% DSS over 56 hours using (1)H NMR spectroscopy. We observed no difference in cell viability as compared to control cultures, and an approximately 1.5-fold increase in IL-6 production upon incubation with 1% DSS. The effect on Caco-2 cell metabolism as measured through changes in the concentration of metabolites in the cell supernatant included a three-fold decrease in the concentration of alanine. Given that the concentrations of other amino acids in the cell culture supernatant were not different between treated and control cultures over 56 hours suggest that DSS inhibits alanine synthesis, specifically alanine aminotransferase, without affecting other key metabolic pathways. The importance of alanine aminotransferase in inflammatory bowel disease is discussed.