Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. To gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics, we sequenced and analyzed nasal (n=229) and oral (n=210) microbiomes with associated health/environmental data from our Wisconsin Infant Study Cohort at age 24-months. Participants with early-life lower respiratory tract infection (LRTI) were more likely to be formula-fed, attend daycare, and experience wheezing. Shotgun metagenomic sequencing with detection of viral and bacterial respiratory pathogens revealed nasal microbiome composition to associate with prior LRTI - namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M. catarrhalis, suggesting interbacterial competition impacts nasal pathogen colonization. This work advances understanding of protective host-microbial interactions occurring in airway microbiomes that alter infection susceptibility in early-life.

中文翻译：

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早期的上呼吸道微生物群与减少下呼吸道感染有关。


介导定植抗性的微生物相互作用在人类微生物组中起着关键作用，从出生开始就塑造了对感染的易感性。为了深入了解微生物组介导的防御和呼吸道病原体定植动力学，我们对鼻腔 （n=229） 和口腔 （n=210） 微生物组以及来自威斯康星州婴儿研究队列的 24 个月大的相关健康/环境数据进行了测序和分析。患有早期下呼吸道感染 （LRTI） 的参与者更有可能接受配方奶喂养、参加日托和经历喘息。霰弹枪法宏基因组测序检测病毒和细菌呼吸道病原体，显示鼻腔微生物组组成与既往 LRTI 相关 - 即较低的 α 多样性、普雷沃氏菌的耗竭和卡他莫拉菌的富集，包括耐药菌株。源自健康微生物组的普雷沃氏菌具有较高的生物合成基因簇丰度，并表现出对卡他分枝杆菌的接触非依赖性抑制，表明细菌间竞争影响鼻部病原体定植。这项工作促进了对气道微生物组中发生的保护性宿主-微生物相互作用的理解，这些相互作用会改变早期感染的易感性。