Microbial, host and xenobiotic diversity in the cystic fibrosis sputum metabolome.
Microbial, host and xenobiotic diversity in the cystic fibrosis sputum metabolome.
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DOI：
10.1038/ismej.2015.207
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发表时间：
2016-06
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囊性纤维化（CF）肺充满了厚厚的粘液，阻塞气道，促进慢性感染。铜绿假单胞菌是该疾病的重要病原体，其产生多种毒性小分子。我们使用基于分子网络的代谢组学来研究CF的化学成分，并评估检测到的微生物分子如何反映患者的微生物组和临床培养史。检测到的代谢物包括外源性物质、铜绿假单胞菌特异性代谢物和宿主鞘脂。临床培养和微生物组特征与在相同样本中检测到铜绿假单胞菌代谢产物不一致。在痰液中检测到的铜绿假单胞菌分子与实验室培养物中的分子不匹配。假单胞菌喹诺酮信号（PQS）很容易从培养菌株中检测到，但不存在于痰液中，即使其前体分子存在。体内PQS产生的缺乏可能是由于CF肺环境的化学性质，表明该病原体的基于培养的研究可能无法解释其在肺中的行为。CF和非CF痰液之间丰度差异最大的分子是鞘脂，包括鞘磷脂、神经酰胺和乳糖神经酰胺。由于这些高度丰富的分子含有炎症介质神经酰胺，它们可能在CF过度炎症中起重要作用。本研究表明CF痰液的化学组成是微生物、宿主和异生物质分子的复杂环境。通过临床培养和16S rRNA基因谱分析检测细菌不一定反映痰液样本中该细菌代谢产物的活跃产生。
Cystic fibrosis (CF) lungs are filled with thick mucus that obstructs airways and facilitates chronic infections. Pseudomonas aeruginosa is a significant pathogen of this disease that produces a variety of toxic small molecules. We used molecular networking-based metabolomics to investigate the chemistry of CF sputa and assess how the microbial molecules detected reflect the microbiome and clinical culture history of the patients. Metabolites detected included xenobiotics, P. aeruginosa specialized metabolites and host sphingolipids. The clinical culture and microbiome profiles did not correspond to the detection of P. aeruginosa metabolites in the same samples. The P. aeruginosa molecules that were detected in sputum did not match those from laboratory cultures. The pseudomonas quinolone signal (PQS) was readily detectable from cultured strains, but absent from sputum, even when its precursor molecules were present. The lack of PQS production in vivo is potentially due to the chemical nature of the CF lung environment, indicating that culture-based studies of this pathogen may not explain its behavior in the lung. The most differentially abundant molecules between CF and non-CF sputum were sphingolipids, including sphingomyelins, ceramides and lactosylceramide. As these highly abundant molecules contain the inflammatory mediator ceramide, they may have a significant role in CF hyperinflammation. This study demonstrates that the chemical makeup of CF sputum is a complex milieu of microbial, host and xenobiotic molecules. Detection of a bacterium by clinical culturing and 16S rRNA gene profiling do not necessarily reflect the active production of metabolites from that bacterium in a sputum sample.