Tuberculosis is a highly infectious and potentially fatal disease accompanied by wasting symptoms, which cause severe metabolic changes in infected people. In this study we have compared the effect of mycobacteria infection on the level of metabolites in blood of humans and mice and whole zebrafish larvae using one highly standardized mass spectrometry pipeline, ensuring technical comparability of the results. Quantification of a range of circulating small amines showed that the levels of the majority of these compounds were significantly decreased in all three groups of infected organisms. Ten of these metabolites were common between the three different organisms comprising: methionine, asparagine, cysteine, threonine, serine, tryptophan, leucine, citrulline, ethanolamine and phenylalanine. The metabolomic changes of zebrafish larvae after infection were confirmed by nuclear magnetic resonance spectroscopy. Our study identified common biomarkers for tuberculosis disease in humans, mice and zebrafish, showing across species conservation of metabolic reprogramming processes as a result of disease. Apparently, the mechanisms underlying these processes are independent of environmental, developmental and vertebrate evolutionary factors. The zebrafish larval model is highly suited to further investigate the mechanism of metabolic reprogramming and the connection with wasting syndrome due to infection by mycobacteria.

中文翻译：

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结核病会导致人类患者，分枝杆菌感染的小鼠和斑马鱼幼虫高度保守的代谢变化

结核病是一种高度传染性疾病，可能致命，并伴有消瘦症状，这些症状会导致受感染者的新陈代谢发生严重变化。在这项研究中，我们使用一种高度标准化的质谱管线比较了分枝杆菌感染对人和小鼠以及整个斑马鱼幼虫血液中代谢物水平的影响，从而确保了结果的技术可比性。对一系列循环中的小胺的定量分析表明，在所有三组感染生物中，大多数这些化合物的水平均显着降低。这些代谢物中的十种在三种不同的生物之间是常见的，包括：蛋氨酸，天冬酰胺，半胱氨酸，苏氨酸，丝氨酸，色氨酸，亮氨酸，瓜氨酸，乙醇胺和苯丙氨酸。核磁共振波谱证实了斑马鱼幼虫感染后的代谢组学变化。我们的研究确定了人类，小鼠和斑马鱼中结核病的常见生物标记物，显示了疾病导致的代谢重编程过程的跨物种保守性。显然，这些过程的基础机制与环境，发育和脊椎动物进化因素无关。斑马鱼幼虫模型非常适合于进一步研究代谢重编程的机制以及与因分枝杆菌感染而导致的虚耗综合症的联系。展示了由于疾病引起的代谢重编程过程的跨物种保护。显然，这些过程的基础机制与环境，发育和脊椎动物进化因素无关。斑马鱼幼虫模型非常适合于进一步研究代谢重编程的机制以及与因分枝杆菌感染而导致的虚耗综合症的联系。展示了由于疾病引起的代谢重编程过程的跨物种保护。显然，这些过程的基础机制与环境，发育和脊椎动物进化因素无关。斑马鱼幼虫模型非常适合于进一步研究代谢重编程的机制以及与因分枝杆菌感染而导致的虚耗综合症的联系。