Respiratory Diseases Group, Murdoch Children's Research Institute, Melbourne, Australia
Department of Respiratory and Sleep Medicine, Royal Children's Hospital, Melbourne, Australia.
Eur Respir J. 2024 May 9;63(5). doi: 10.1183/13993003.02290-2023. Print 2024 May.
In cystic fibrosis, gastrointestinal dysfunction and lower airway infection occur early and are independently associated with poorer outcomes in childhood. This study aimed to define the relationship between the microbiota at each niche during the first 2 years of life, its association with growth and airway inflammation, and explanatory features in the metabolome.
67 bronchoalveolar lavage fluid (BALF), 62 plasma and 105 stool samples were collected from 39 infants with cystic fibrosis between 0 and 24 months who were treated with prophylactic antibiotics. 16S rRNA amplicon and shotgun metagenomic sequencing were performed on BALF and stool samples, respectively; metabolomic analyses were performed on all sample types. Sequencing data from healthy age-matched infants were used as controls.
Bacterial diversity increased over the first 2 years in both BALF and stool, and microbial maturation was delayed in comparison to healthy controls from the RESONANCE cohort. Correlations between their respective abundance in both sites suggest stool may serve as a noninvasive alternative for detecting BALF and . Multisite metabolomic analyses revealed age- and growth-related changes, associations with neutrophilic airway inflammation, and a set of core systemic metabolites. BALF abundance was correlated with altered stool microbiome composition and systemic metabolite alterations, highlighting a complex gut-plasma-lung interplay and new targets with therapeutic potential.
Exploration of the gut-lung microbiome and metabolome reveals diverse multisite interactions in cystic fibrosis that emerge in early life. Gut-lung metabolomic links with airway inflammation and abundance warrant further investigation for clinical utility, particularly in non-expectorating patients.
在囊性纤维化中，胃肠道功能障碍和下呼吸道感染很早就会发生，并且与儿童时期的预后较差独立相关。本研究旨在定义生命最初 2 年内每个生态位的微生物群之间的关系，其与生长和气道炎症的关联，以及代谢组学中的解释特征。
39 例囊性纤维化婴儿在 0 至 24 个月期间接受预防性抗生素治疗，收集了 67 份支气管肺泡灌洗液（BALF）、62 份血浆和 105 份粪便样本。对 BALF 和粪便样本分别进行 16S rRNA 扩增子和 shotgun 宏基因组测序；对所有样本类型进行代谢组学分析。使用来自健康年龄匹配婴儿的测序数据作为对照。
在 BALF 和粪便中，细菌多样性在最初 2 年内增加，与来自 RESONANCE 队列的健康对照组相比，微生物成熟延迟。两个部位的相对丰度之间的相关性表明粪便可能是一种替代支气管肺泡灌洗检测的非侵入性方法。多部位代谢组学分析显示出年龄和生长相关的变化，与中性粒细胞性气道炎症相关，以及一组核心系统性代谢物。BALF 丰度与改变的粪便微生物群组成和系统性代谢物改变相关，突出了肠道-血浆-肺的复杂相互作用以及具有治疗潜力的新靶点。
对肠道-肺微生物组和代谢组的探索揭示了囊性纤维化中早期出现的多样化多部位相互作用。肠道-肺代谢组学与气道炎症和丰度的联系需要进一步研究以评估其临床应用价值，特别是在非排痰患者中。
