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: 10200667
• 负责人: Suman Ranjan Das
• 金额: $ 21.25万
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200667
• 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; infant infection; metagenomic sequencing; metatranscriptome; metatranscriptomics; microbial; microbial community; microbial genomics; microbiome; microbiome composition; microbiome signature; microbiota; multidisciplinary; 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.

概括 生命早期呼吸道微生物组的变化似乎对罹患此病的风险产生重大影响 呼吸道疾病，包括婴儿感染和复发性喘息疾病。目前没有初级 这些疾病的预防策略。婴儿期的急性呼吸道疾病 (ARIs)，尤其是 呼吸道合胞病毒 (RSV) 是众所周知的儿童哮喘危险因素。我们的初步数据 表明急性 RSV 感染期间鼻咽部存在乳杆菌和葡萄球菌 与保护第二年喘息结果有关，尽管这些背后的机制 协会在很大程度上仍不为人所知。了解这些关系可能会导致以下方面的发展： 儿童哮喘发展的一级预防策略。我们的假设是具体的 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，随后预防复发性喘息的发生和 儿童哮喘。为了解决我们的假设，在目标 1 中，我们计划使用宏基因组测序来 在来自出生队列的现有鼻洗样本中在物种水平上表征 URT 微生物组群落 首次捕获婴儿 RSV 感染，并每年评估复发性喘息疾病。在目标 2 中， 我们将进行宏转录组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）通过转录组介导对 RSV 介导的喘息的保护 基于分子途径的分析。拟议的研究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（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引领未来 制定一级预防策略以减少婴儿急性呼吸系统疾病发病率和后续发病率 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 （例如，乳杆菌属或乳杆菌属的组合）作为免疫生物干预来改善 RSV 介导生命早期的急性和慢性呼吸系统结局。