季节性气道微生物群与转录组相互作用促进儿童哮喘发作
2022/02/28
摘要
背景：尽管哮喘患儿呼吸系统疾病和恶化的季节性变化已得到很好地描述，但在这些事件中上呼吸道微生物是否发挥季节特异性作用尚不清楚。
目的：我们假设鼻部微生物群组成是季节性动态的，并且离散的微生物-宿主的相互作用以季节特异性的方式改变哮喘恶化的风险。
方法：在所有季节中，收集呼吸系统健康期间（基线，n=181份样本）或首次罹患呼吸系统疾病（n=97份）期间来自易恶化的哮喘患儿重复的鼻腔样本，进行细菌（16S rRNA基因）和真菌（ITS2）生物标志物测序。病毒检测通过多重PCR进行。配对的鼻转录组数据用于季节性动态和综合分析。
结果：上呼吸道细菌和真菌微生物群和鼻病毒检测显示出明显的季节动态。在经季节调整的分析中，基线和呼吸道疾病微生物群的变化与随后的病情恶化相关。特别是在秋季，呼吸道疾病及恶化事件最常见，一些莫拉色菌和嗜血杆菌成员在病毒阳性呼吸道疾病及其疾病恶化中均得到丰富。由链球菌或葡萄球菌组成的两个离散细菌网络的丰度，与哮喘恶化相关的SMAD3鼻上皮转录模块表现出相反的相互作用，显著增加了随后恶化的几率[OR=14.7，95%CI：1.50-144，P=0.02；OR=39.17，95% CI：2.44-626，P=0.008]。
结论：上呼吸道微生物群随季节及呼吸系统疾病和哮喘发作的季节性趋势而变化。季节调整分析揭示了特定的细菌-宿主相互作用，该相互作用显著增加了儿童哮喘恶化的风险。
(中日友好医院呼吸与危重症医学科 王静茹 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2022 Feb 8;S0091-6749(22)00146-4.doi:10.1016/j.jaci.2022.01.020. )
Seasonal Airway Microbiome and Transcriptome Interactions Promote Childhood Asthma Exacerbations
Kathryn E McCauley, Kaitlin Flynn, Vincent DiMassa, Brandon LaMere, Douglas W Fadrosh, Kole V Lynch, Michelle A Gill, Jacqueline A Pongracic, Gurjit K Khurana Hershey, Carolyn M Kercsmar, Andrew H Liu, Christine C Johnson, Haejin Kim, Meyer Kattan, George T O'Connor, Leonard B Bacharier, Stephen J Teach, Peter J Gergen, Lisa M Wheatley, Alkis Togias, Petra LeBeau, Agustin Calatroni, Scott Presnell, Homer A Boushey, William W Busse, James E Gern, Daniel J Jackson, Matthew C Altman, Susan V Lynch, National Institute of Allergy and Infectious Diseases-sponsored Inner-City Asthma Consortium
Abstract
BACKGROUND：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.
OBJECTIVE:We hypothesized that nasal microbiota composition is seasonally dynamic and that discrete microbial-host interactions modify risk of asthma exacerbation in a season-specific manner.
METHODS：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 rRNA gene) and fungal (ITS2) biomarker sequencing. Virus detection was performed by multiplex PCR. Paired nasal transcriptome data was examined for seasonal dynamics and integrative analyses.
RESULTS：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 viral positive respiratory illnesses and those that progressed to exacerbations. The abundance of two discrete bacterial networks, characteristically comprising either Streptococcus or Staphylococcus exhibited opposing interactions with an exacerbation-associated SMAD3 nasal epithelial transcriptional module to significantly increase odds of subsequent exacerbation [OR=14.7, 95% CI: 1.50-144, P=0.02; OR=39.17, 95% CI: 2.44-626, P=0.008, respectively].
CONCLUSIONS：Upper airway microbiomes co-vary with season and with seasonal trends in respiratory illnesses and asthma exacerbations. Seasonally-adjusted analyses reveal specific bacterial-host interactions that significantly increase risk of asthma exacerbation in these children.
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miR-144-3p是一种与严重糖皮质激素依赖性哮喘相关的生物标志物
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磁共振成像评估哮喘患者支气管壁厚度
