Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients.
Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients.
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DOI：
10.1371/journal.pone.0040221
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kaufmann SH
中科院分区：
文献类型：
--
作者：
Weiner J 3rd;Parida SK;Maertzdorf J;Black GF;Repsilber D;Telaar A;Mohney RP;Arndt-Sullivan C;Ganoza CA;Faé KC;Walzl G;Kaufmann SH
虽然结核病造成的死亡人数比任何其他病原体都多，但大多数感染的人都携带着没有疾病迹象的病原体。我们研究了未感染者、潜伏感染者和活动性结核病患者血清中bbb400小分子的代谢组学。我们发现了氨基酸、脂质和核苷酸代谢途径的变化，为结核病抗炎代谢变化提供了证据。代谢谱显示吲哚胺2,3双加氧酶1 （IDO1）活性增加，磷脂酶活性降低，腺苷代谢产物丰度增加，以及与潜伏感染相比，活动性疾病中纤维化病变的指标。与我们的预测一致，我们通过实验证明了结核病诱导的IDO1活性。此外，我们证明了代谢谱和细胞因子信号传导之间的联系。最后，我们发现20种代谢物足以对结核病患者和健康个体进行强有力的区分。我们的结果为结核病的生物学提供了具体的见解，并为结核病代谢生物标志物的合理开发铺平了道路。
Although tuberculosis (TB) causes more deaths than any other pathogen, most infected individuals harbor the pathogen without signs of disease. We explored the metabolome of >400 small molecules in serum of uninfected individuals, latently infected healthy individuals and patients with active TB. We identified changes in amino acid, lipid and nucleotide metabolism pathways, providing evidence for anti-inflammatory metabolomic changes in TB. Metabolic profiles indicate increased activity of indoleamine 2,3 dioxygenase 1 (IDO1), decreased phospholipase activity, increased abundance of adenosine metabolism products, as well as indicators of fibrotic lesions in active disease as compared to latent infection. Consistent with our predictions, we experimentally demonstrate TB-induced IDO1 activity. Furthermore, we demonstrate a link between metabolic profiles and cytokine signaling. Finally, we show that 20 metabolites are sufficient for robust discrimination of TB patients from healthy individuals. Our results provide specific insights into the biology of TB and pave the way for the rational development of metabolic biomarkers for TB.
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