1 Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, the Netherlands.
2 Spaarne Gasthuis Academy, Hoofddorp, the Netherlands.
Am J Respir Crit Care Med. 2017 Dec 15;196(12):1582-1590. doi: 10.1164/rccm.201703-0554OC.
Perinatal and postnatal influences are presumed important drivers of the early-life respiratory microbiota composition. We hypothesized that the respiratory microbiota composition and development in infancy is affecting microbiota stability and thereby resistance against respiratory tract infections (RTIs) over time.
To investigate common environmental drivers, including birth mode, feeding type, antibiotic exposure, and crowding conditions, in relation to respiratory tract microbiota maturation and stability, and consecutive risk of RTIs over the first year of life.
In a prospectively followed cohort of 112 infants, we characterized the nasopharyngeal microbiota longitudinally from birth on (11 consecutive sample moments and the maximum three RTI samples per subject; in total, n = 1,121 samples) by 16S-rRNA gene amplicon sequencing.
Using a microbiota-based machine-learning algorithm, we found that children experiencing a higher number of RTIs in the first year of life already demonstrate an aberrant microbial developmental trajectory from the first month of life on as compared with the reference group (0-2 RTIs/yr). The altered microbiota maturation process coincided with decreased microbial community stability, prolonged reduction of Corynebacterium and Dolosigranulum, enrichment of Moraxella very early in life, followed by later enrichment of Neisseria and Prevotella spp. Independent drivers of these aberrant developmental trajectories of respiratory microbiota members were mode of delivery, infant feeding, crowding, and recent antibiotic use.
Our results suggest that environmental drivers impact microbiota development and, consequently, resistance against development of RTIs. This supports the idea that microbiota form the mediator between early-life environmental risk factors for and susceptibility to RTIs over the first year of life.
围产期和产后的影响被认为是生命早期呼吸微生物群落组成的重要驱动因素。我们假设婴儿期的呼吸微生物群落组成和发育会影响微生物群落的稳定性，从而影响呼吸道感染（RTIs）的发生风险。
研究常见的环境驱动因素，包括分娩方式、喂养类型、抗生素暴露和拥挤条件，与呼吸道微生物群落的成熟和稳定性以及生命最初一年内 RTIs 的连续发生风险的关系。
在一个前瞻性随访的 112 例婴儿队列中，我们通过 16S-rRNA 基因扩增子测序，从出生开始对鼻咽微生物群进行了纵向特征分析（11 个连续的样本时间点和每个受试者最多 3 个 RTI 样本；总共 n=1121 个样本）。
使用基于微生物组的机器学习算法，我们发现生命最初一年内经历更多 RTIs 的儿童，与参考组（0-2 次/年）相比，从第一个月起就已经表现出异常的微生物发育轨迹。微生物群成熟过程的改变与微生物群落稳定性的降低、Corynebacterium 和 Dolosigranulum 的减少、Moraxella 非常早的富集以及随后 Neisseria 和 Prevotella spp 的富集同时发生。这些呼吸道微生物成员异常发育轨迹的独立驱动因素包括分娩方式、婴儿喂养、拥挤和最近使用抗生素。
我们的结果表明，环境驱动因素会影响微生物群的发育，从而影响对 RTIs 发展的抵抗力。这支持了这样一种观点，即微生物群是生命最初一年内早期生活环境危险因素与 RTIs 易感性之间的中介。
