Sitkin S I, Tkachenko E I, Vakhitov T Ia, Oreshko L S, Zhigalova T N
Eksp Klin Gastroenterol. 2013(12):44-57.
Metabolomics is the emerging science of measurement and analysis of metabolome--the complete set of low molecular weight compounds in a cell, tissue, organ or whole organism. One of the aims of metabolomics is to research the response of an organism to a pathophysiological insult by measuring the concentrations of small molecule metabolites in biofluids and tissues and its dynamics. Intestinal microbiota is most probably involved in the development and maintenance of autoimmune inflammation in ulcerative colitis and celiac disease. Gas chromatography-mass spectrometry (GC - MS) of serum generates comprehensive metabolic profiles, reflecting integrated human (systemic) and gut microbial metabolism which may be altered in disease states. The aim of this study was to investigate GC - MS-based serum metabolomic profiles in UC and CD patients. Serum metabolic profiles were collected from 75 individuals: 20 patients with mild-moderate active UC, 35 CD patients, and 20 healthy controls (HC). We characterized 84 serum metabolites by use GC-MS. 18 metabolites at least have a combined (human + microbial) origin. In serum of UC patients, phenylacetic acid (PAA), 4-hydroxyphenylacetic acid (4-HPAA), 3-indolylacetic acid (IAA), succinic acid (SA) and fumaric acid (FA) were the metabolites most prominently increased, whereas 3-phenylpropionic acid (PPA) was significantly decreased. Serum of CD patients showed significant increases in IAA, 3-indolepropionic acid (IPA), SA and FA. Increased serum levels of succinic acid suggest its possible damaging effect on intestinal mucosa especially in ulcerative colitis. Orally administered butyrate + inulin as supplement to mesalazine in UC or gluten free diet in CD was effective in reducing disease activity with a marked improvement of serum metabolomic profiles (including SA reduction) and gut microbiota in both diseases. There were no any adverse events.
代谢组学是一门新兴的科学,用于测量和分析代谢组,即细胞、组织、器官或整个生物体中低分子量化合物的完整集合。代谢组学的目标之一是通过测量生物流体和组织中小分子代谢物的浓度及其动态变化,研究生物体对病理生理损伤的反应。肠道微生物群很可能参与了溃疡性结肠炎和乳糜泻中自身免疫性炎症的发生和维持。血清气相色谱-质谱联用(GC-MS)可生成全面的代谢图谱,反映人类(全身)和肠道微生物代谢的综合情况,而这些代谢情况在疾病状态下可能会发生改变。本研究的目的是调查基于GC-MS的溃疡性结肠炎(UC)和克罗恩病(CD)患者的血清代谢组学图谱。收集了75名个体的血清代谢图谱:20例轻-中度活动性UC患者、35例CD患者和20名健康对照(HC)。我们使用GC-MS对84种血清代谢物进行了表征。18种代谢物至少具有混合(人类+微生物)来源。在UC患者的血清中,苯乙酸(PAA)、4-羟基苯乙酸(4-HPAA)、3-吲哚乙酸(IAA)、琥珀酸(SA)和富马酸(FA)是最显著增加的代谢物,而3-苯丙酸(PPA)则显著降低。CD患者的血清中IAA、3-吲哚丙酸(IPA)、SA和FA显著增加。血清琥珀酸水平升高表明其可能对肠黏膜有损害作用,尤其是在溃疡性结肠炎中。在UC患者中,口服丁酸盐+菊粉作为美沙拉嗪的补充剂,或在CD患者中采用无麸质饮食,可有效降低疾病活动度,显著改善两种疾病的血清代谢组学图谱(包括SA降低)和肠道微生物群。未出现任何不良事件。