Age and antibiotic use influence longitudinal dynamics of the upper respiratory microbiome in children with recurrent acute otitis media

年龄和抗生素使用会影响复发性急性中耳炎患儿上呼吸道微生物群的纵向动态变化。

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Abstract

The upper respiratory tract (URT) microbiome has emerged as a key component of acute otitis media (AOM) pathophysiology; however, few studies conducted to date have evaluated URT microbiome composition in children with recurrent AOM (rAOM). We collected serial nasopharyngeal samples from a cohort of 58 children, 6 to 35 months of age, over a one-year period. Samples were analyzed using 16S rRNA sequencing and PCR-based assays for common otopathogens and respiratory viruses. Age was strongly associated with differential abundance of specific genera, including increased abundance of genera associated with respiratory health (e.g., Dolosigranulum, Corynebacterium). In contrast, samples collected during AOM episodes or within 30 days of receipt of an antibiotic had a lower relative abundance of these genera. Further, the number of antibiotic-free days prior to sample collection was associated with global changes in microbiome composition. Unsupervised clustering identified three microbiome profiles that differed by incidence of AOM, bacterial otopathogen burden, symptom score, and number of antibiotic-free days prior to sample collection. Increasing age was associated with transition to profiles characterized by lower incidence of AOM and bacterial otopathogen burden, while antibiotic use was associated with transition to a profile associated with greater incidence of AOM. Our findings indicate that alterations of the microbiome associated with aging may contribute to decreased incidence of AOM as children age, while systemic antibiotic use may induce dysbiosis, thereby enhancing AOM susceptibility. IMPORTANCE: Ear infections are the most common bacterial infection among young children and the leading cause of healthcare visits and antibiotic prescriptions. This study explores the connection between the microbiome of the nose-the community of microorganisms that live in different areas of the human body-and recurrent ear infections in young children. An analysis of nasal swabs collected from 58 children over a year showed that as children age, they tend to have fewer bacterial pathogens and more species that are associated with a healthy state in their microbiomes. These more mature microbiomes were associated with fewer ear infections. In contrast, recent use of antibiotics was associated with microbiomes that had more bacterial pathogens and that were associated with greater ear infection incidence. Overall, these findings indicate that the microbiome may be a key factor in reduced ear infections as children age.

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