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 Pseudomonas and Veillonella. Multisite metabolomic analyses revealed age- and growth-related changes, associations with neutrophilic airway inflammation, and a set of core systemic metabolites. BALF Pseudomonas 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 Pseudomonas 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发生较早，并且与儿童期较差的预后独立相关。本研究旨在明确生命前两年每个生态位微生物群之间的关系、其与生长和气道炎症的关系以及代谢组的解释特征。

研究人员从 39 名 0 至 24 个月大的囊性纤维化婴儿中采集了 67 份支气管肺泡灌洗液 (BALF)、62 份血浆和 105 份粪便样本，这些婴儿接受了预防性抗生素治疗。分别对 BALF 和粪便样本进行 16S rRNA 扩增子和鸟枪法宏基因组测序；对所有样品类型进行代谢组学分析。来自健康年龄匹配婴儿的测序数据用作对照。

头两年内，BALF 和粪便中的细菌多样性均有所增加，并且与 RESONANCE 队列中的健康对照相比，微生物成熟被延迟。两个部位各自丰度之间的相关性表明粪便可以作为检测 BALF假单胞菌和韦荣球菌的非侵入性替代方法。多位点代谢组学分析揭示了与年龄和生长相关的变化、与中性粒细胞气道炎症的关联以及一组核心全身代谢物。 BALF假单胞菌丰度与粪便微生物组成的改变和全身代谢物的改变相关，突出了复杂的肠道-血浆-肺相互作用和具有治疗潜力的新靶点。

对肠肺微生物组和代谢组的探索揭示了生命早期出现的囊性纤维化的多种多位点相互作用。肠肺代谢组学与气道炎症和假单胞菌丰度之间的联系值得进一步研究其临床实用性，特别是在非咳痰患者中。