Metabonomic investigation of human Schistosoma mansoni infection

Metabonomic investigation of human Schistosoma mansoni infection
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DOI:
10.1039/c0mb00262c
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发表时间:
2011-01-01
影响因子:
--
通讯作者:
Deelder, Andre M.
Deelder, Andre M.
中科院分区:
生物3区
文献类型:
--
作者:
Balog, Crina I. A.;Meissner, Axel;Deelder, Andre M.

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血吸虫病是一种寄生虫感染,在许多热带和亚热带发展中国家流行,主要影响农村地区超过 2.07 亿人。就社会经济和公共卫生而言,它是继疟疾之后第二重要的寄生虫感染。在分子水平上研究宿主-寄生虫相互作用以及识别感染和感染相关发病率的生物标志物对于改进治疗和发病率控制策略具有重要价值。为此,我们进行了一项基于核磁共振 (NMR) 的代谢组学研究,研究对象为来自乌干达维多利亚湖附近农村地区的 447 名个体,该地区曼氏血吸虫患病率很高,该物种主要分布在非洲,包括马达加斯加和南美洲部分地区。在吡喹酮 (PZQ) 化疗之前和之后(一次或两次)的五个时间点从个体收集队列样本。通过对记录的一维 (1D) NMR 谱进行有监督的多变量统计分析,我们能够根据尿液特征的差异区分两个年龄组(儿童和成人)中的感染者和未感染者。研究发现,曼氏链球菌感染的潜在分子标志物主要与肠道菌群、能量代谢和肝功能的变化有关。这些发现与早期关于实验动物曼氏沙门氏菌感染的研究数据一致,从而为这种感染特有的代谢反应的存在提供了确凿的证据。
Schistosomiasis is a parasitic infection that is endemic in many developing countries in the tropics and subtropics afflicting more than 207 million people primarily in rural areas. After malaria, it is the second most important parasitic infection in terms of socio-economic and public health. Investigation of the host-parasite interaction at the molecular level and identification of biomarkers of infection and infection-related morbidity would be of value for improved strategies for treatment and morbidity control. To this end, we conducted a nuclear magnetic resonance (NMR) based metabonomics study involving a well-characterized cohort of 447 individuals from a rural area in Uganda near Lake Victoria with a high prevalence of Schistosoma mansoni, a species predominantly occurring in Africa including Madagascar and parts of South America. Cohort samples were collected from individuals at five time-points, before and after (one or two times) chemotherapy with praziquantel (PZQ). Using supervised multivariate statistical analysis of the recorded one-dimensional (1D) NMR spectra, we were able to discriminate infected from uninfected individuals in two age groups (children and adults) based on differences in their urinary profiles. The potential molecular markers of S. mansoni infection were found to be primarily linked to changes in gut microflora, energy metabolism and liver function. These findings are in agreement with data from earlier studies on S. mansoni infection in experimental animals and thus provide corroborating evidence for the existence of metabolic response specific for this infection.