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Lessons learned from metabolomics in cystic fibrosis
Molecular and Cellular Pediatrics ( IF 2.4 ) Pub Date : 2015-10-20 , DOI: 10.1186/s40348-015-0020-8
Marianne S Muhlebach 1 , Wei Sha 2
Affiliation  

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.

中文翻译:

囊性纤维化代谢组学的经验教训

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,其中慢性细菌感染导致支气管扩张并最终导致呼吸衰竭。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) 的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。代谢组学已显示血液基质、呼出气和呼吸道上皮培养物的 CF 与非 CF 的区别,每种都显示不同的途径。对支气管肺泡灌洗液和呼出气冷凝物的研究表明,每项研究的作者都与炎症相关的代谢物分离,从而解决了肺部疾病的严重性;例如,乙醇、丙酮、嘌呤。脂质组学已应用于血液和痰样本,显示出与肺功能和铜绿假单胞菌感染状态的关联。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。从全局代谢组学分析的意义上说,代谢组学是一种强大的技术,可以发现以前未涉及 CF 的途径。除了 CF 中脂质代谢的已知差异之外,这些可能包括嘌呤、线粒体途径和葡萄糖代谢的不同方面。然而,有必要进行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。评估细菌来源代谢物的研究尚处于早期阶段。因此,可以设想进一步设计良好的研究。
更新日期:2015-10-20
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