Lessons learned from metabolomics in cystic fibrosis.
Lessons learned from metabolomics in cystic fibrosis.
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DOI：
10.1186/s40348-015-0020-8
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Sha W
中科院分区：
文献类型：
--
作者：
Muhlebach MS;Sha W
囊性纤维化是一种单基因多系统疾病；然而，呼吸道表现导致主要的发病率和死亡率，慢性细菌感染导致支气管扩张和最终呼吸衰竭。代谢组学允许使用不同的质谱方法对样品中的代谢过程进行相对完整的快照。迄今为止，用于发现囊性纤维化（CF）生物标志物或病理机制的样本类型包括血液、呼吸道分泌物和呼出气体。代谢组学显示，血液、呼出气体和呼吸道上皮培养物的基质有CF与非CF的区别，每种基质都有不同的途径。肺部疾病的严重程度已经通过研究支气管肺泡灌洗和呼出冷凝水来解决，这些研究显示代谢物与炎症有关；例如，乙醇、丙酮、嘌呤。脂质组学已应用于与肺功能和铜绿假单胞菌感染状态相关的血液和痰样本。最后，体外培养细菌的研究表明，细菌代谢物的差异与临床参数有关。代谢组学，在全球代谢组学分析的意义上，是一项强大的技术，它允许发现以前未涉及CF的途径。这些途径可能包括嘌呤，线粒体途径，除了CF中已知的脂质代谢差异之外，葡萄糖代谢的不同方面。然而，有针对性的研究来验证这些潜在的代谢物和感兴趣的途径是必要的。评估细菌来源代谢物的研究尚处于早期阶段。因此，可以设想进一步精心设计的研究。
Cystic fibrosis is a mono-genetic multi-system disease; however, respiratory manifestations cause the main morbidity and mortality where chronic bacterial infections lead to bronchiectasis and ultimately respiratory failure. Metabolomics allows a relatively complete snapshot of metabolic processes in a sample using different mass spectrometry methods. Sample types used for discovery of biomarkers or pathomechanisms in cystic fibrosis (CF) have included blood, respiratory secretions, and exhaled breath to date. Metabolomics has shown distinction of CF vs. non-CF for matrices of blood, exhaled breath, and respiratory epithelial cultures, each showing different pathways. Severity of lung disease has been addressed by studies in bronchoalveolar lavage and exhaled breath condensate showing separation by metabolites that the authors of each study related to inflammation; e.g., ethanol, acetone, purines. Lipidomics has been applied to blood and sputum samples showing associations with lung function and Pseudomonas aeruginosa infection status. Finally, studies of bacteria grown in vitro showed differences of bacterial metabolites to be associated with clinical parameters. Metabolomics, in the sense of global metabolomic profiling, is a powerful technique that has allowed discovery of pathways that had not previously been implicated in CF. These may include purines, mitochondrial pathways, and different aspects of glucose metabolism besides the known differences in lipid metabolism in CF. However, targeted studies to validate such potential metabolites and pathways of interest are necessary. Studies evaluating metabolites of bacterial origin are in their early stages. Thus further well-designed studies could be envisioned.