Elucidating the role of nasopharyngeal microbiome in Respiratory Syncytial Virus associated diseases in children

摘要 呼吸道微生物组的早期生命变化似乎对发病风险有重大影响。 呼吸道疾病，包括婴儿感染和反复出现的喘息性疾病。当前没有主服务器 针对这些疾病的预防策略。婴儿期的急性呼吸道疾病(ARI)，特别是在 呼吸道合胞病毒(RSV)是儿童哮喘的一个众所周知的危险因素。我们的初步数据 提示呼吸道合胞病毒急性感染时鼻咽中存在乳杆菌和葡萄球菌。 对第二年的喘息结果有保护作用，尽管背后的机制 这种关联在很大程度上仍不为人所知。了解这些关系可能会导致 儿童哮喘发展的初级预防策略。我们的假设是， 城市轨道交通微生物群落功能(S)及其相互作用调节宿主免疫反应 在RSV ARI期间和之后，随后防止复发的喘息和 儿童哮喘。为了解决我们的假设，在目标1中，我们计划使用元基因组测序来 年出生队列中现有鼻腔冲洗样本中URT微生物群落的物种水平特征 捕获了第一个婴儿呼吸道合胞病毒感染，并每年评估反复出现的喘息性疾病。在目标2中， 我们将进行元转录分析，以了解乳杆菌和其他城市轨道交通的机制 微生物组(如葡萄球菌)通过转录组介导对RSV介导的喘息的保护作用 基于分子途径的分析。这项拟议中的研究将是第一次使用元基因组学进行研究 和转录后测序，以描述早期生命微生物组(在RSV感染期间)并研究其 与儿童哮喘发展的相互作用。这个项目的结果可能会通向未来 制定初级预防策略，以减少婴儿急性呼吸道发病率和随后的发病率 儿童哮喘。此外，这项研究将为使用特定细菌种类的临床试验奠定坚实的基础。 (如乳杆菌属Lactobacilla spp.或乳杆菌的组合。)作为一种免疫生物学干预措施来改善 呼吸道合胞病毒介导的早期急性和慢性呼吸结局。

SUMMARY Early-life changes in the respiratory microbiome appear to have a substantial impact on the risk of developing respiratory morbidity, including infant infections and recurrent wheezing illnesses. There are currently no primary preventive strategies for these disorders. Acute respiratory illnesses (ARIs) during infancy, particularly with Respiratory Syncytial Virus (RSV) are a well-known risk factor for childhood asthma. Our preliminary data suggests that presence of Lactobacillus and Staphylococcus in nasopharynx during acute RSV infection is associated to be protective for the year 2 wheezing outcomes, although the mechanisms behind these associations remain largely unknown. Understanding these relationships could lead to the development of primary prevention strategies for the development of childhood asthma. Our hypothesis is that specific function(s) of URT microbiome community, and their interactions modulate host immune responses during and following RSV ARI, subsequently protecting against development of recurrent wheeze and childhood asthma. To address our hypotheses, in Aim 1, we plan to use metagenomic sequencing to characterize URT microbiome community at species level in existing nasal wash samples from a birth cohort in which first infant RSV infection is captured, and recurrent wheezing illnesses are assessed annually. In Aim 2, we will perform metatranscriptomic analysis to understand mechanism of Lactobacillus and other URT microbiome (e.g., Staphylococcus) mediated protection of RSV mediated wheezing through transcriptome- based analysis of molecular pathways. The proposed investigation will be the first study to use metagenomic and metatranscriptomic sequencing to describe the early-life microbiome (during RSV infection) and to study its interactions with the development of childhood asthma. Results from this project could lead to the future development of primary prevention strategies to reduce acute infant respiratory morbidity and subsequent childhood asthma. Further, this study will establish a strong basis for clinical trials to use specific bacteria species (e.g., Lactobacillus spp. or a combination of Lactobacillus spp.) as an immunobiotic intervention to ameliorate RSV mediated early-life acute and chronic respiratory outcomes.