Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
PLoS One. 2013 Jul 9;8(7):e67654. doi: 10.1371/journal.pone.0067654. Print 2013.
Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD). The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate data analysis was employed to assess differences in metabolomic profiles that occurred as a consequence of IBD development and severity (at week 20). These changes were contrasted to those that occurred as a consequence of gender. Our results demonstrate that both IL-10 gene-deficient and wild-type mice exhibit gender-related changes in urinary metabolomic profile over time. Some male-female separating metabolites are common to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to be related predominantly to gender maturation. In addition, we were able to identify gender-separating metabolites that are unique for IL-10 gene-deficient and wild-type mice and, therefore, may be indicative of a gender-specific involvement in the development and severity of the intestinal inflammation. The comparison of the gender-separating metabolomic profile from IL-10 gene-deficient mice and wild-type mice during the development of IBD allowed us to identify changes in profile patterns that appear to be imperative in the development of intestinal inflammation, but yet central to gender-related differences in IBD development. The knowledge of metabolomic profile differences by gender and by disease severity has potential clinical implications in the design of both biomarkers of disease as well as the development of optimal therapies.
代谢组学分析可用于研究炎症性肠病（IBD）中疾病引起的变化。本研究旨在探讨男性和女性在发生 IBD 时代谢组特征的差异。采用 IL-10 基因缺陷型 IBD 小鼠模型和野生型小鼠，分别在 4、6、8、12、16 和 20 周龄时收集尿液，并用核磁共振（NMR）光谱法进行分析。采用多变量数据分析评估由于 IBD 发展和严重程度（在 20 周时）而导致的代谢组特征差异。这些变化与由于性别而发生的变化进行了对比。我们的结果表明，IL-10 基因缺陷型和野生型小鼠的尿液代谢组特征均随时间发生与性别相关的变化。一些雄性和雌性分离的代谢物在 IL-10 基因缺陷型和对照野生型小鼠中均存在，因此似乎主要与性别成熟有关。此外，我们还能够鉴定出 IL-10 基因缺陷型和野生型小鼠特有的性别分离代谢物，因此可能表明它们在肠道炎症的发展和严重程度中具有性别特异性参与。在 IBD 发展过程中比较 IL-10 基因缺陷型和野生型小鼠的性别分离代谢组特征，使我们能够识别出似乎对肠道炎症发展至关重要的特征模式变化，但又与 IBD 发展中的性别差异有关。对性别和疾病严重程度相关的代谢组特征差异的了解，在疾病生物标志物的设计以及最佳治疗方法的开发方面具有潜在的临床意义。
