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

阐明鼻咽微生物组在儿童呼吸道合胞病毒相关疾病中的作用

• 批准号: 10057650
• 负责人: Suman Ranjan Das
• 金额: $ 25.5万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-23 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10057650
• 关键词: 16S ribosomal RNA sequencing; 2 year old; Acute; Address; Allergic Disease; Animals; Asthma; Bacteria; Biological; Birth; Child; Childhood; Childhood Asthma; Chronic; Climacteric; Clinical Trials; Communities; Data; Development; Disease; Environmental Risk Factor; Future; Gene Expression; Genes; Genetic; Genus staphylococcus; Goals; Hospitalization; Immune; Immune response; Infant; Infection; Intervention; Investigation; Knowledge; Lactobacillus; Lead; Life; Lower Respiratory Tract Infection; Lung diseases; Lung infections; Mediating; Metabolic Pathway; Metagenomics; Molecular Analysis; Nasopharynx; Nose; Nursery Schools; Outcome; Pathway interactions; Pattern; Phenotype; Play; Predisposition; Prevention strategy; Primary Prevention; Publishing; Recurrence; Research Design; Research Personnel; Respiratory Syncytial Virus Infections; Respiratory syncytial virus; Rhinovirus; Risk; Risk Factors; Role; Sampling; Severities; Statistical Data Interpretation; Structure; Taxonomy; Techniques; Testing; Transcript; United States; United States National Institutes of Health; Upper respiratory tract; Virus Diseases; Wheezing; base; cohort; cytokine; design; epidemiology study; improved; infancy; metagenomic sequencing; metatranscriptome; metatranscriptomics; microbial; microbial community; microbial genomics; microbiome; microbiome composition; microbiota; multidisciplinary; neonatal infection; novel; protective effect; respiratory; respiratory microbiome; respiratory morbidity; transcriptome; working group

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.

总结 呼吸道微生物组的早期变化似乎对发生呼吸道疾病的风险有重大影响。 呼吸道疾病，包括婴儿感染和反复喘息疾病。目前没有主要的 这些疾病的预防策略。婴儿期急性呼吸道疾病（阿里斯），尤其是 呼吸道合胞病毒（RSV）是众所周知的儿童哮喘的危险因素。我们的初步数据 提示在急性RSV感染期间鼻咽中存在乳酸杆菌和葡萄球菌， 相关的是保护第2年喘息的结果，虽然这些背后的机制， 相关性在很大程度上仍然未知。理解这些关系可以导致 儿童哮喘发展的一级预防策略。我们的假设是 URT微生物群落的功能及其相互作用调节宿主免疫反应 在RSV ARI期间和之后，随后防止复发性喘息的发展， 儿童哮喘为了解决我们的假设，在目标1中，我们计划使用宏基因组测序， 在物种水平上表征来自出生队列的现有鼻洗液样本中的URT微生物群落， 第一个婴儿RSV感染被捕获，并每年评估复发性喘息疾病。在目标2中， 我们将进行元转录组学分析，以了解乳酸菌和其他URT的机制 微生物组（例如，葡萄球菌）通过转录组介导的RSV介导的喘息保护作用- 基于分子途径的分析。拟议的调查将是第一个使用宏基因组学的研究。 和元转录组测序来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。该项目的成果可能会导致未来 制定一级预防战略，以减少婴儿急性呼吸道疾病发病率和 儿童哮喘此外，这项研究将为使用特定细菌物种的临床试验建立强有力的基础 (e.g.,乳杆菌属或乳杆菌属的组合）作为一种免疫生物干预， RSV介导的早期急性和慢性呼吸结局。