Center for Infectious Diseases and Immunology, Research Institute, Rochester General Hospital, Rochester, NY, 14621, USA.
Department of Microbiology & Immunology, Centers for Genomic Sciences and Advanced Microbial Processing, Drexel University College of Medicine, 245 N 15th Street, Philadelphia, PA, 19102, USA.
Int J Pediatr Otorhinolaryngol. 2021 Apr;143:110629. doi: 10.1016/j.ijporl.2021.110629. Epub 2021 Jan 21.
About 10-15% children develop frequent acute otitis media (AOM) confirmed by tympanocentesis. These children are designated sOP (stringently defined otitis-prone) because all AOM episodes have been microbiologically confirmed. The cause of otitis-proneness in sOP children is multi-factorial, including frequent otopathogen nasopharyngeal (NP) colonization and deficiency in innate and adaptive immune responses. A largely unexplored contributor to otitis proneness is NP microbiome composition. Since the microbiome modulates otopathogen NP colonization and immune responses, we hypothesized that the NP microbiome composition in sOP children might be dysregulated.
We performed 16S rRNA sequencing to analyze microbiome composition in 157 NP samples from 28 sOP and 68 AOM-free children when they were 6 months or 12 months old and healthy. Bioinformatic approaches were employed to examine the composition difference between the two populations and its correlation with changes in levels of inflammatory cytokines.
A different global microbiome profile and reduced alpha diversity was observed in the NP microbiome of sOP children when 6 months old, compared with that from AOM-free children of the same age. This difference was resolved when groups were compared at 12 months old. We found 4 bacterial genera-Bacillus, Veillonella, Gemella, and Prevotella-correlated with higher levels of pro-inflammatory cytokines in the NP. Those 4 bacterial genera were in lower abundance in sOP compared to AOM-free children.
Dysbiosis occurs in the NP microbiome of sOP children at an early age even when they were healthy. This dysbiosis correlates with a lower inflammatory state in the NP of these children.
约 10-15% 的儿童会频繁发生经鼓室穿刺术确诊的急性中耳炎（AOM）。这些儿童被指定为 sOP（严格定义的易患中耳炎），因为所有 AOM 发作均经微生物学确认。sOP 儿童易患中耳炎的原因是多因素的，包括频繁的鼻咽部（NP）病原体定植和先天及适应性免疫反应缺陷。NP 微生物组组成是一个很大程度上尚未被探索的易患中耳炎的因素。由于微生物组调节病原体 NP 定植和免疫反应，我们假设 sOP 儿童的 NP 微生物组组成可能失调。
我们对 28 名 sOP 儿童和 68 名无 AOM 儿童的 157 个 NP 样本进行了 16S rRNA 测序，以分析微生物组组成。当他们 6 个月或 12 个月大且健康时，采用生物信息学方法来检查两个群体之间的组成差异及其与炎症细胞因子水平变化的相关性。
与同龄无 AOM 儿童相比，sOP 儿童的 NP 微生物组在 6 个月大时表现出不同的全球微生物组谱和较低的α多样性。当在 12 个月龄时比较两组时，这种差异得到解决。我们发现 4 个细菌属——芽孢杆菌、韦荣球菌属、孪生球菌属和普雷沃氏菌属——与 NP 中促炎细胞因子水平升高相关。与无 AOM 儿童相比，这 4 个细菌属在 sOP 中丰度较低。
即使在健康状态下，sOP 儿童的 NP 微生物组在早期就出现了失调。这种失调与这些儿童 NP 中的炎症状态较低相关。
