Frey Dario L, Bridson Calum, Dittrich Susanne, Graeber Simon Y, Stahl Mirjam, Wege Sabine, Herth Felix, Sommerburg Olaf, Schultz Carsten, Dalpke Alexander, Mall Marcus A, Boutin Sébastien
Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany.
Front Microbiol. 2022 May 13;13:885822. doi: 10.3389/fmicb.2022.885822. eCollection 2022.
Airway inflammation and microbiome dysbiosis are hallmarks of cystic fibrosis () lung disease. However, longitudinal studies are needed to decipher which factors contribute to the long-term evolution of these key features of We therefore evaluated the relationship between fluctuation in microbiome and inflammatory parameters in a longitudinal study including a short- (1-year) and a long-term (3+ years) period. We collected 118 sputum samples from 26 adult patients and analyzed them by 16S rRNA gene sequencing. We measured the levels of inflammatory cytokines, neutrophil elastase, and anti-proteinases; lung function (FEV1% predicted); and BMI. The longitudinal evolution was analyzed based on (i) the rates of changes; (ii) the intra-patient stability of the variables; and (iii) the dependency of the rates of changes on the baseline values. We observed that the diversity of the microbiome was highly variable over a 1-year period, while the inflammatory markers showed a slower evolution, with significant changes only observed in the 3+ year cohort. Further, the degree of fluctuation of the biomass and the dominance of the microbiome were associated with changes in inflammatory markers, especially IL-1β and IL-8. This longitudinal study demonstrates for the first time that the long-term establishment and periodical variation of the abundance of a dominant pathogen is associated with a more severe increase in inflammation. This result indicates that a single time point or 1-year study might fail to reveal the correlation between microbial evolution and clinical degradation in cystic fibrosis.
气道炎症和微生物群失调是囊性纤维化（CF）肺部疾病的标志。然而，需要进行纵向研究来解读哪些因素促成了CF这些关键特征的长期演变。因此，我们在一项纵向研究中评估了微生物群波动与炎症参数之间的关系，该研究包括一个短期（1年）和一个长期（3年以上）阶段。我们从26名成年CF患者中收集了118份痰样本，并通过16S rRNA基因测序进行分析。我们测量了炎症细胞因子、中性粒细胞弹性蛋白酶和抗蛋白酶的水平；肺功能（预测FEV1%）；以及体重指数（BMI）。基于以下方面分析纵向演变：（i）变化率；（ii）变量在患者内的稳定性；以及（iii）变化率对基线值的依赖性。我们观察到，微生物群的多样性在1年期间高度可变，而炎症标志物的演变较慢，仅在3年以上的队列中观察到显著变化。此外，生物量的波动程度和微生物群的优势与炎症标志物的变化相关，尤其是白细胞介素-1β（IL-1β）和白细胞介素-8（IL-8）。这项纵向研究首次表明，优势病原体丰度的长期建立和周期性变化与炎症更严重的增加相关。这一结果表明，单一时间点或1年的研究可能无法揭示囊性纤维化中微生物演变与临床恶化之间的相关性。
