Relationship between airway dysbiosis, inflammation and lung function in adults with cystic fibrosis,Journal of Cystic Fibrosis

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Relationship between airway dysbiosis, inflammation and lung function in adults with cystic fibrosis
Journal of Cystic Fibrosis ( IF 5.4 ) Pub Date : 2021-01-08 , DOI: 10.1016/j.jcf.2020.12.022
Dario L Frey ₁ , Sébastien Boutin ₂ , Susanne A Dittrich ₃ , Simon Y Graeber ₄ , Mirjam Stahl ₅ , Sabine Wege ₆ , Felix J F Herth ₇ , Olaf Sommerburg ₈ , Carsten Schultz ₉ , Marcus A Mall ₄ , Alexander H Dalpke ₁₀

Affiliation

Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany.
Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany.
Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany; Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany.
Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany; Division of Pediatric Pulmonology & Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany; Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany; German Center for Lung Research (DZL), associated partner site, Berlin, Germany.
Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany; Division of Pediatric Pulmonology & Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany; Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), associated partner site, Berlin, Germany.
Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany.
Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany.
Translational Lung Research Center (TLRC), Heidelberg, Germany; Division of Pediatric Pulmonology & Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.
Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, USA.
Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany; Institute of Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany.

Airway dysbiosis has been associated with lung disease severity in patients with cystic fibrosis (CF). However, the relationship between dysbiosis, airway inflammation and lung function impairement remains poorly understood. The aim of this study was therefore to determine how the structure of the sputum microbiota, airway inflammation markers and spirometry are related in patients with CF.

Sputum samples were collected from 106 CF patients between 12 and 72 years. These were analyzed by 16S rRNA gene amplicon sequencing. Moreover, levels of pro-inflammatory cytokines (IL-1β, IL-8, IL-6 and TNF-α) and Neutrophil elastase (NE) were determined. The relationship between the microbiota, inflammation markers and forced expiratory volume in one second percent predicted (FEV₁% predicted) was evaluated by multi-parameter analysis.

The microbiota α-diversity correlated inverse with inflammation markers IL-1β, IL-8, TNF-α, NE and positively with FEV₁% predicted. Patients could be divided into 7 clusters based on their microbiota structure. The most diverse cluster was defined by oropharyngeal-like flora (OF) while the others were characterized by the dominance of a single pathogen. Patients with the diverse OF microbiota cluster had lower sputum inflammatory markers and higher FEV₁% predicted compared to patients with a pathogen-dominated microbiota including Pseudomonas aeruginosa.

Our results suggest that the diversity of the airway microbiota is an important biomarker of the severity of airway inflammation linking dysbiosis to lung function decline in patients with CF.

中文翻译：

囊性纤维化成人气道生态失调、炎症和肺功能的关系

气道生态失调与囊性纤维化 (CF) 患者的肺部疾病严重程度有关。然而，生态失调、气道炎症和肺功能损害之间的关系仍然知之甚少。因此，本研究的目的是确定 CF 患者的痰微生物群结构、气道炎症标志物和肺活量测定是如何相关的。

从 106 名 12 至 72 岁的 CF 患者中收集痰液样本。这些通过16S rRNA基因扩增子测序进行分析。此外，测定了促炎细胞因子（IL-1β、IL-8、IL-6 和 TNF-α）和中性粒细胞弹性蛋白酶（NE）的水平。通过多参数分析评估微生物群、炎症标志物和用力呼气量之间的关系（预测的 1 秒百分比（FEV _{1 % 预测））。}

微生物群 α 多样性与炎症标志物 IL-1β、IL-8、TNF-α、NE 呈负相关，与 FEV ₁ % 预测值呈正相关。患者可根据其微生物群结构分为 7 个集群。最多样化的集群是由口咽样菌群 (OF) 定义的，而其他集群的特点是单一病原体的优势。与具有包括铜绿假单胞菌在内的以病原体为主的微生物群的患者相比，具有多样化 OF 微生物群簇的患者的痰炎症标志物较低，预测的 FEV ₁ % 较高。

我们的研究结果表明，气道微生物群的多样性是气道炎症严重程度的重要生物标志物，将菌群失调与 CF 患者的肺功能下降联系起来。

更新日期：2021-01-08

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