Dept of Child Health, School of Medicine, Cardiff University, Cardiff, UK.
Joint first authors.
Eur Respir J. 2020 May 7;55(5). doi: 10.1183/13993003.01909-2019. Print 2020 May.
Chronic lung disease of prematurity (CLD), also called bronchopulmonary dysplasia, is a major consequence of preterm birth, but the role of the microbiome in its development remains unclear. Therefore, we assessed the progression of the bacterial community in ventilated preterm infants over time in the upper and lower airways, and assessed the gut-lung axis by comparing bacterial communities in the upper and lower airways with stool findings. Finally, we assessed whether the bacterial communities were associated with lung inflammation to suggest dysbiosis.
We serially sampled multiple anatomical sites including the upper airway (nasopharyngeal aspirates), lower airways (tracheal aspirate fluid and bronchoalveolar lavage fluid) and the gut (stool) of ventilated preterm-born infants. Bacterial DNA load was measured in all samples and sequenced using the V3-V4 region of the 16S rRNA gene.
From 1102 (539 nasopharyngeal aspirates, 276 tracheal aspirate fluid, 89 bronchoalveolar lavage, 198 stool) samples from 55 preterm infants, 352 (32%) amplified suitably for 16S RNA gene sequencing. Bacterial load was low at birth and quickly increased with time, but was associated with predominant operational taxonomic units (OTUs) in all sample types. There was dissimilarity in bacterial communities between the upper and lower airways and the gut, with a separate dysbiotic inflammatory process occurring in the lower airways of infants. Individual OTUs were associated with increased inflammatory markers.
Taken together, these findings suggest that targeted treatment of the predominant organisms, including those not routinely treated, such as spp., may decrease the development of CLD in preterm-born infants.
早产儿慢性肺病(CLD),也称为支气管肺发育不良,是早产儿的主要后果,但微生物组在其发展中的作用尚不清楚。因此,我们评估了通气早产儿的上、下呼吸道中细菌群落随时间的进展,并通过比较上、下呼吸道的细菌群落与粪便发现来评估肠-肺轴。最后,我们评估了细菌群落是否与肺部炎症有关,以提示失调。
我们连续采集了包括上呼吸道(鼻咽抽吸物)、下呼吸道(气管抽吸液和支气管肺泡灌洗液)和肠道(粪便)在内的多个解剖部位的多个通气早产儿的样本。对所有样本均进行细菌 DNA 负荷测量,并使用 16S rRNA 基因的 V3-V4 区进行测序。
从 55 名早产儿的 1102 个(539 个鼻咽抽吸物、276 个气管抽吸液、89 个支气管肺泡灌洗液、198 个粪便)样本中,352 个(32%)适合进行 16S RNA 基因测序。出生时细菌负荷较低,且随时间迅速增加,但与所有样本类型中的主要分类单元(OTUs)相关。上、下呼吸道和肠道之间的细菌群落存在差异,婴儿下呼吸道存在单独的失调性炎症过程。个体 OTUs 与炎症标志物的增加相关。
总的来说,这些发现表明,针对主要生物体的靶向治疗,包括那些常规不治疗的生物体,如 spp.,可能会减少早产儿 CLD 的发生。