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比较肠易激综合征患者、溃疡性结肠炎患者和健康对照者的代谢组学特征:对病理生理学和潜在生物标志物的新认识。

Comparison of the metabolomic profiles of irritable bowel syndrome patients with ulcerative colitis patients and healthy controls: new insights into pathophysiology and potential biomarkers.

机构信息

Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.

出版信息

Aliment Pharmacol Ther. 2019 Mar;49(6):723-732. doi: 10.1111/apt.15141. Epub 2019 Jan 31.

Abstract

BACKGROUND

Evaluation of the metabolomic profile of patients with irritable bowel syndrome offers an opportunity to identify novel pathophysiological targets and biomarkers that could discriminate this disorder from related conditions.

AIM

To identify potential urinary biomarkers that discriminate irritable bowel syndrome patients from ulcerative colitis patients in remission and healthy controls and to explore the pathophysiology of irritable bowel syndrome using a metabolomic approach.

METHODS

Urine samples were collected from 39 irritable bowel syndrome patients, 53 ulcerative colitis patients in clinical remission and 21 healthy controls. Urinary metabolites were identified and quantified using direct infusion/liquid chromatography tandem mass spectrometry and gas-chromatography mass spectrometry.

RESULTS

Patients with irritable bowel syndrome had a unique urinary metabolome that could separate them from ulcerative colitis patients with an area under the curve = 0.99 (95% confidence interval 0.95-1.00). The most important metabolites for this separation were a group of amino acids and organic acids. In addition, subjects with irritable bowel syndrome could be discriminated from healthy controls using their metabolic fingerprints. Irritable bowel syndrome patients had lower urinary Phosphatidyl choline acyl-alkyl C38:6, dopamine and p-hydroxybenzoic acid than healthy controls. Levels of some urinary metabolites including histamine correlated significantly with irritable bowel syndrome symptom severity scores.

CONCLUSIONS

Irritable bowel syndrome patients have a unique urinary metabolomic profile compared to ulcerative colitis patients in clinical remission or healthy subjects. These data suggest that metabolomic profiling may provide important insights into pathophysiology and testable biomarkers to discriminate irritable bowel syndrome from other disorders that can mimic this condition and can be used to assess its severity and identify potential novel pathophysiological pathways.

摘要

背景

评估肠易激综合征患者的代谢组学特征为识别新的病理生理靶点和生物标志物提供了机会,这些靶点和标志物可将该疾病与相关疾病区分开来。

目的

鉴定潜在的尿生物标志物,以区分缓解期溃疡性结肠炎患者和健康对照者中的肠易激综合征患者,并采用代谢组学方法探讨肠易激综合征的病理生理学。

方法

收集 39 例肠易激综合征患者、53 例溃疡性结肠炎缓解期患者和 21 例健康对照者的尿样。采用直接进样/液相色谱串联质谱法和气相色谱-质谱法鉴定和定量尿液代谢物。

结果

肠易激综合征患者具有独特的尿代谢组学特征,可通过曲线下面积(AUC)=0.99(95%置信区间 0.95-1.00)将其与溃疡性结肠炎患者区分开来。用于这种分离的最重要的代谢物是一组氨基酸和有机酸。此外,肠易激综合征患者可通过其代谢指纹与健康对照者区分开来。与健康对照者相比,肠易激综合征患者的尿磷酰胆碱酰基-烷基 C38:6、多巴胺和对羟基苯甲酸的水平较低。一些尿代谢物的水平,包括组氨酸,与肠易激综合征症状严重程度评分显著相关。

结论

与临床缓解期溃疡性结肠炎患者或健康受试者相比,肠易激综合征患者具有独特的尿代谢组学特征。这些数据表明,代谢组学分析可能为病理生理学提供重要见解,并为可区分肠易激综合征与可模拟该疾病的其他疾病的生物标志物提供可检验的方法,并可用于评估其严重程度和识别潜在的新病理生理途径。

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