Panorganismal metabolic response modeling of an experimental Echinostoma caproni infection in the mouse.
Panorganismal metabolic response modeling of an experimental Echinostoma caproni infection in the mouse.
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DOI：
10.1021/pr900185s
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发表时间：
2009-08
影响因子：
4.4
通讯作者：
Utzinger J
中科院分区：
文献类型：
--
作者：
Saric J;Li JV;Wang Y;Keiser J;Veselkov K;Dirnhofer S;Yap IK;Nicholson JK;Holmes E;Utzinger J
寄生虫感染期间宿主组织和生物流体的代谢谱可以揭示新的生物标志物信息，并有助于阐明疾病的机制。实验性山羊棘口线虫感染的多室代谢效应已在12只远交雌性小鼠中进行了表征，这些小鼠经口感染了30只山羊棘口线虫。Caproni囊蚴，使用另外12只未感染的动物作为对照组。感染后36天处死小鼠，取出脑、肠（结肠、回肠、空肠）、肾、肝和脾。使用高分辨率魔角旋转1H NMR光谱法测量组织样品的代谢概况，并通过应用常规1H NMR光谱法测量生物流体。光谱数据进行了分析，通过主成分分析，偏最小二乘推导的方法和层次投影分析。使用分层建模和相关性分析，将组织中预防诱导的代谢变化与生物体液（尿液、血浆、粪便水）中代谢物浓度的改变相关联。在肝脏、肾皮质、肠组织中确定了感染的代谢描述符，但在脾脏、脑或肾髓质中未确定。在小鼠中观察到的主要生理变化是小肠吸收不良，这通过回肠中各种氨基酸（例如丙氨酸、牛磺酸、谷氨酰胺和支链氨基酸）的水平降低来证明。此外，肠道微生物活性或组成的改变反映在结肠中三甲胺水平的增加。我们的建模方法有助于深入评估不同生物基质代谢谱的协变，并发现尿液和血浆最能反映回肠隔室的变化。最后，E. Caproni感染不仅导致直接的局部（回肠和空肠）效应，而且还引起远端代谢变化（结肠和几个外周器官），因此描述了感染的全生物体代谢反应。肠吸虫棘口吸虫caproni代表了一个理想的模式寄生虫研究亚病理变化的小鼠宿主。我们提出了一个多房室评估的组织和生物液体，使用1H NMR光谱，以获得一个整体的代谢观点的感染。应用一种新的层次聚类算法与传统的多变量方法，有利于解释的系统性生化变化，表现出本地化和远程的影响，在主机。
Metabolic profiling of host tissues and biofluids during parasitic infections can reveal new biomarker information and aid the elucidation of mechanisms of disease. The multicompartmental metabolic effects of an experimental Echinostoma caproni infection have been characterized in 12 outbred female mice infected orally with 30 E. caproni metacercariae each, using a further 12 uninfected animals as a control group. Mice were killed 36 days postinfection and brain, intestine (colon, ileum, jejeunum), kidney, liver, and spleen were removed. Metabolic profiles of tissue samples were measured using high-resolution magic angle spinning 1H NMR spectroscopy and biofluids measured by applying conventional 1H NMR spectroscopy. Spectral data were analyzed via principal component analysis, partial least-squares-derived methods and hierarchical projection analyses. Infection-induced metabolic changes in the tissues were correlated with altered metabolite concentrations in the biofluids (urine, plasma, fecal water) using hierarchical modeling and correlation analyses. Metabolic descriptors of infection were identified in liver, renal cortex, intestinal tissues but not in spleen, brain or renal medulla. The main physiological change observed in the mouse was malabsorption in the small intestine, which was evidenced by decreased levels of various amino acids in the ileum, for example, alanine, taurine, glutamine, and branched chain amino acids. Furthermore, altered gut microbial activity or composition was reflected by increased levels of trimethylamine in the colon. Our modeling approach facilitated in-depth appraisal of the covariation of the metabolic profiles of different biological matrices and found that urine and plasma most closely reflected changes in ileal compartments. In conclusion, an E. caproni infection not only results in direct localized (ileum and jejenum) effects, but also causes remote metabolic changes (colon and several peripheral organs), and therefore describes the panorganismal metabolic response of the infection. The intestinal fluke Echinostoma caproni represents an ideal model parasite for investigating subpathologic changes in the murine host. We present a multicompartmental assessment of tissues and biofluids using 1H NMR spectroscopy to obtain a holistic metabolic view of the infection. Application of a novel hierarchical cluster algorithm together with conventional multivariate approaches facilitates interpretation of the systemic biochemical changes demonstrating both localized and remote effects in the host.
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DOI：
10.1124/jpet.103.057109
发表时间：
2004-03-01
影响因子：
3.5
作者：
Hatanaka, T;Haramura, M;Ganapathy, ME
通讯作者：
Ganapathy, ME
影响因子：
2.2
作者：
JAMES, TL;MCDONALD, GG
通讯作者：
MCDONALD, GG
DOI：
10.1016/s1479-666x(05)80043-5
发表时间：
2005-06-01
影响因子：
2.5
作者：
Lai, ECH;Lau, WY
通讯作者：
Lau, WY
影响因子：
11.2
作者：
Kennedy, Peter G. E.
通讯作者：
Kennedy, Peter G. E.
影响因子：
7.4
作者：
Cloarec, O;Dumas, ME;Nicholson, J
通讯作者：
Nicholson, J