WS08.06Integrative computational analysis of longitudinal effects of elexacaftor/tezacaftor/ivacaftor on sputum microbiome and proteome in patients with cystic fibrosis

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.539

L. Schaupp , R.L. Knoll , K. Fentker , J. Nazat Martinez Medina , M. Riabchenko , V.H. Jarquín-Díaz , A. Löwe , J. Duerr , M. Stahl , P. Mertins , S. Boutin , S.Y. Graeber , S.K. Forslund-Startceva , M.A. Mall

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引用次数: 0

Abstract

Objectives

Despite beneficial effects of CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) on the airway microbiome and inflammation in CF patients, residual airway infection and inflammation persist at a level expected to contribute to progressive lung damage over time. The aim of this project was therefore to initiate an integrative computational analysis to identify novel biomarkers and therapeutic targets for persisting airway infection and inflammation.

Methods

Sputum samples were collected from CF patients with at least one F508del allele, aged 12 years and older, before and at 1, 3 and 12 months after ETI initiation and subjected to microbiome, proteomic and inflammation marker analysis. An integrative data analysis was used to determine the relationship between clinical covariates, proteomic and inflammatory measures and the microbial composition.

Results

Sputum mesh-pore size, free NE activity (P≤0.01), sweat chloride concentration and free CatG activity (P≤0.05) most strongly influenced the airway microbiota composition. Commensal bacteria correlated positively with FEV₁ and negatively with inflammation markers and sputum viscoelasticity. CF pathogens, like Pseudomonas, showed opposite associations and could be linked to immune/inflammatory processes. PERMANOVA revealed that time after treatment had a more significant effect on proteomic (R2=6.2%, P=0.001) than on microbiome profiles (R2=2.5%, P=0.004).

Conclusion

Our integrated multi-omics analysis provides initial insights into bacteria-protein associations on ETI therapy. Distinctive association patterns between pathogens and commensals with clinical parameters were observed. Further exploration is required to identify novel biomarkers linked to persisting airway infection and inflammation in CF patients treated with ETI.

Funded by the German Research Foundation (SFB 1449 – project ID 431232613) and German Federal Ministry of Education and Research (82DZL009C1).

查看原文本刊更多论文

ws08.06 . elexaftor /tezacaftor/ivacaftor对囊性纤维化患者痰微生物组和蛋白质组纵向影响的综合计算分析

尽管CFTR调节剂治疗对CF患者气道微生物组和炎症有有益的影响，但随着时间的推移，残留的气道感染和炎症持续存在，预计会导致进行性肺损伤。因此，该项目的目的是启动综合计算分析，以确定持续气道感染和炎症的新型生物标志物和治疗靶点。方法收集年龄在12岁及以上且至少有一个F508del等位基因的CF患者在ETI开始前、开始后1、3和12个月的痰样本，进行微生物组学、蛋白质组学和炎症标志物分析。综合数据分析用于确定临床协变量、蛋白质组学和炎症指标与微生物组成之间的关系。结果痰网孔大小、游离NE活性（P≤0.01）、汗液氯离子浓度和游离CatG活性（P≤0.05）对气道微生物群组成影响最大。共生菌与FEV1呈正相关，与炎症标志物和痰黏弹性呈负相关。CF病原体，如假单胞菌，表现出相反的关联，可能与免疫/炎症过程有关。PERMANOVA显示，治疗后时间对蛋白质组学（R2=6.2%， P=0.001）的影响大于对微生物组谱（R2=2.5%， P=0.004）的影响。结论我们的综合多组学分析初步揭示了细菌-蛋白在ETI治疗中的关联。观察到病原体和共生菌与临床参数之间的独特关联模式。需要进一步探索与接受ETI治疗的CF患者持续气道感染和炎症相关的新生物标志物。由德国研究基金会（SFB 1449 -项目ID 431232613）和德国联邦教育与研究部（82DZL009C1）资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.