Department of Medicine, University of California, San Francisco, Calif.
Systems Immunology Program, Benaroya Research Institute, Seattle, Wash.
J Allergy Clin Immunol. 2022 Jul;150(1):204-213. doi: 10.1016/j.jaci.2022.01.020. Epub 2022 Feb 8.
Seasonal variation in respiratory illnesses and exacerbations in pediatric populations with asthma is well described, though whether upper airway microbes play season-specific roles in these events is unknown.
We hypothesized that nasal microbiota composition is seasonally dynamic and that discrete microbe-host interactions modify risk of asthma exacerbation in a season-specific manner.
Repeated nasal samples from children with exacerbation-prone asthma collected during periods of respiratory health (baseline; n = 181 samples) or first captured respiratory illness (n = 97) across all seasons, underwent bacterial (16S ribosomal RNA gene) and fungal (internal transcribed spacer region 2) biomarker sequencing. Virus detection was performed by multiplex PCR. Paired nasal transcriptome data were examined for seasonal dynamics and integrative analyses.
Upper airway bacterial and fungal microbiota and rhinovirus detection exhibited significant seasonal dynamics. In seasonally adjusted analysis, variation in both baseline and respiratory illness microbiota related to subsequent exacerbation. Specifically, in the fall, when respiratory illness and exacerbation events were most frequent, several Moraxella and Haemophilus members were enriched both in virus-positive respiratory illnesses and those that progressed to exacerbations. The abundance of 2 discrete bacterial networks, characteristically comprising either Streptococcus or Staphylococcus, exhibited opposing interactions with an exacerbation-associated SMAD3 nasal epithelial transcriptional module to significantly increase the odds of subsequent exacerbation (odds ratio = 14.7, 95% confidence interval = 1.50-144, P = .02; odds ratio = 39.17, 95% confidence interval = 2.44-626, P = .008, respectively).
Upper airway microbiomes covary with season and with seasonal trends in respiratory illnesses and asthma exacerbations. Seasonally adjusted analyses reveal specific bacteria-host interactions that significantly increase risk of asthma exacerbation in these children.
儿童哮喘患者的呼吸道疾病和病情恶化存在季节性变化，这一点已有充分描述，不过上呼吸道微生物是否在这些事件中发挥特定于季节的作用尚不清楚。
我们假设鼻微生物群落组成具有季节性动态变化，且微生物与宿主的离散相互作用以特定于季节的方式改变哮喘恶化的风险。
在所有季节中，患有易发生恶化的哮喘的儿童在呼吸道健康期（基线；n=181 个样本）或首次出现呼吸道疾病时（n=97 个样本）反复采集鼻样本，进行细菌（16S 核糖体 RNA 基因）和真菌（内部转录间隔区 2）生物标志物测序。通过多重 PCR 进行病毒检测。检查配对的鼻转录组数据以确定季节性动态变化并进行综合分析。
上呼吸道细菌和真菌微生物群以及鼻病毒检测显示出明显的季节性动态变化。在季节调整分析中，基线和呼吸道疾病微生物群的变化均与随后的恶化有关。具体而言，在秋季，呼吸道疾病和恶化事件最为频繁时，呼吸道疾病中病毒阳性且进展为恶化的样本中，莫拉菌属和嗜血菌属的多个成员增多。2 个不同的细菌网络的丰度，通常由链球菌或葡萄球菌组成，与与恶化相关的 SMAD3 鼻上皮转录模块呈相反的相互作用，显著增加随后恶化的几率（比值比=14.7，95%置信区间=1.50-144，P=0.02；比值比=39.17，95%置信区间=2.44-626，P=0.008）。
上呼吸道微生物组与季节以及呼吸道疾病和哮喘恶化的季节性趋势相关。季节调整分析显示，特定的细菌-宿主相互作用显著增加了这些儿童哮喘恶化的风险。
