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支气管扩张症患者呼吸道微生物群组成及全身炎症生物标志物的研究进展

Insights into respiratory microbiome composition and systemic inflammatory biomarkers of bronchiectasis patients.

作者信息

Konovalovas Aleksandras, Armalytė Julija, Klimkaitė Laurita, Liveikis Tomas, Jonaitytė Brigita, Danila Edvardas, Bironaitė Daiva, Mieliauskaitė Diana, Bagdonas Edvardas, Aldonytė Rūta

机构信息

Life Sciences Center, Institute of Biosciences, Vilnius University, Vilnius, Lithuania.

State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.

出版信息

Microbiol Spectr. 2024 Nov 13;12(12):e0414423. doi: 10.1128/spectrum.04144-23.

Abstract

UNLABELLED

The human microbiomes, including the ones present in the respiratory tract, are described and characterized in an increasing number of studies. However, the composition and the impact of the healthy and/or impaired microbiome on pulmonary health and its interaction with the host tissues remain enigmatic. In chronic airway diseases, bronchiectasis stands out as a progressive condition characterized by microbial colonization and infection. In this study, we aimed to investigate the microbiome of the lower airways and lungs of bronchiectasis patients together with their serum cytokine and chemokine content, and gain novel insights into the pathogenesis of bronchiectasis. The microbiome of 47 patients was analyzed by sequencing of full-length 16S rRNA gene using amplicon sequencing Oxford Nanopore technologies. Their serum inflammatory mediators content was quantified in parallel. Several divergently composed microbiome groups were identified and characterized, the majority of patients displayed one dominant bacterial species, whereas others had a more diverse microbiome. The analysis of systemic immune biomarkers revealed two distinct inflammatory response groups, i.e., low and high response groups, each associated with a specific array of clinical symptoms, microbial composition, and diversity. Moreover, we have identified some microbiome compositions associated with high inflammatory response, i.e., high levels of pro- and anti-inflammatory cytokines, whereas other microbiomes were in correlation with low inflammatory responses. Although bronchiectasis pathogenetic mechanisms remain to be elucidated, it is clear that addressing microbiome composition in the airways is a valuable resource not only for diagnosis but also for personalized disease management.

IMPORTANCE

The population of microorganisms on/in the human body resides in distinct local microbiomes, including the respiratory microbiome. It remains unclear what defines a healthy and a diseased respiratory microbiome. We investigated the respiratory microbiome in chronic pulmonary infectious disease, i.e., bronchiectasis, and researched correlations between microbiome composition, systemic inflammatory biomarkers, and disease characteristics. The bronchoalveolar microbiome of 47 patients was sequenced, and their serum inflammatory mediators were quantified. The microbiomes were grouped based on their content and diversity. In addition, patients were also grouped into low- and high-response groups according to their inflammatory biomarkers' levels. Certain microbiome compositions, mainly single-species dominated, were associated with high levels of inflammatory cytokines, whereas others correlated with low inflammatory response and remained diverse. We conclude that respiratory microbiome composition is a valuable resource for the diagnostics and personalized management of bronchiectasis, which may include preserving microbiome diversity and introducing possible probiotics.

摘要

未标注

越来越多的研究对人类微生物群进行了描述和特征分析,包括呼吸道中的微生物群。然而,健康和/或受损微生物群对肺部健康的组成、影响及其与宿主组织的相互作用仍然是个谜。在慢性气道疾病中,支气管扩张作为一种以微生物定植和感染为特征的进行性疾病脱颖而出。在本研究中,我们旨在调查支气管扩张患者下呼吸道和肺部的微生物群及其血清细胞因子和趋化因子含量,以获得对支气管扩张发病机制的新见解。使用牛津纳米孔技术通过全长16S rRNA基因测序分析了47例患者的微生物群。同时对他们血清中的炎症介质含量进行了定量分析。鉴定并表征了几个组成不同的微生物群组,大多数患者表现出一种优势细菌物种,而其他患者的微生物群则更加多样化。对全身免疫生物标志物的分析揭示了两个不同的炎症反应组,即低反应组和高反应组,每组都与一系列特定的临床症状、微生物组成和多样性相关。此外,我们还确定了一些与高炎症反应相关的微生物群组成,即促炎和抗炎细胞因子水平较高,而其他微生物群则与低炎症反应相关。尽管支气管扩张的发病机制仍有待阐明,但很明显,研究气道中的微生物群组成不仅对诊断有价值,而且对个性化疾病管理也有价值。

重要性

人体内外的微生物群体存在于不同的局部微生物群中,包括呼吸道微生物群。目前尚不清楚是什么定义了健康和患病的呼吸道微生物群。我们研究了慢性肺部感染性疾病即支气管扩张中的呼吸道微生物群,并研究了微生物群组成、全身炎症生物标志物和疾病特征之间的相关性。对47例患者的支气管肺泡微生物群进行了测序,并对他们血清中的炎症介质进行了定量分析。根据微生物群的含量和多样性对其进行分组。此外,根据患者炎症生物标志物的水平,将患者也分为低反应组和高反应组。某些微生物群组成,主要是单一物种占主导,与高水平的炎症细胞因子相关,而其他微生物群则与低炎症反应相关且保持多样化。我们得出结论,呼吸道微生物群组成是支气管扩张诊断和个性化管理的宝贵资源,这可能包括保持微生物群多样性和引入可能的益生菌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e749/11619244/d87257be5214/spectrum.04144-23.f001.jpg

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