Respiratory Tract Microbiota and Acute Otitis Media Development in Young Infants

小婴儿呼吸道微生物群和急性中耳炎的发育

基本信息

批准号：
8766556
负责人：
Tasnee Chonmaitree
金额：
$ 15.44万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-12-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8766556
关键词：
Acute Age Age-Months Antibiotics Area Bacteria Birth Child Childhood Chronic Clinical Data Communicable Diseases Communities Complement Complex Complication Data Development Diagnosis Disease Enrollment Environment Eustachian Tube Functional disorder Future Genetic Goals Haemophilus influenzae Health High Prevalence Infant Inflammation Inflammatory Response Institution Intervention Invaded Laboratories Lead Life Longitudinal Studies Lung diseases Medical Medicine Mentors Metagenomics Methods Moraxella (Branhamella) catarrhalis Morbidity - disease rate Nasopharynx Natural History Operative Surgical Procedures Otitis Otitis Media Outcome Pathogenesis Pattern Physicians Play Predisposition Prevention Probiotics Public Health Recovery Recurrence Relative (related person)Research Respiratory System Respiratory Tract Infections Respiratory tract structure Risk Risk Factors Role Sampling Scientist Societies Specimen Sterility Streptococcus Streptococcus pneumoniae Supervision Swab Symptoms Taxon Techniques Texas Time Training Transplantation Universities Upper Respiratory Infections Upper respiratory tract Vagina Viral Virus Virus Diseases age related base cohort college commensal microbes design experience follow-up gastrointestinal innovation member microbial community microbiome middle ear novel pathogen pathogenic bacteria prevent programs prospective pyrosequencing rRNA Genes respiratory success virus development virus pathogenesis

项目摘要

DESCRIPTION (provided by applicant): Otitis Media is one of the most common diseases seen in pediatric practice and the most frequent reason children consume antibiotics or undergo surgery. Acute otitis media (AOM) is a polymicrobial disease and its pathogenesis involves complex interactions between bacteria, viruses, and the host inflammatory response. The disease mostly occurs as a complication of viral upper respiratory tract infection (URI). AOM bacterial pathogens colonize the respiratory tract but do no harm until viral URI occurs; the URI-associated inflammation leads to dysfunction of the Eustachian tube, which facilitates entry of the colonized bacterial pathogens and/or URI virus into the middle ear. The upper respiratory tract is sterile at birth, but infants gradually acquire complex bacterial communities during the first months of life. Several hundred different types of bacteria, both pathogens and commensals, can potentially colonize the upper respiratory tract. Early colonization with AOM bacterial pathogens is highly associated with early AOM onset and recurrent and chronic otitis later in life. Data have shown interactions among colonizing bacterial pathogens and competition between pathogen- and commensal- colonization in the nasopharynx. One way to prevent bacterial AOM is to reduce pathogen colonization by enhancing commensal colonization. To reach this goal, a better understanding of the complex interactions of the nasopharyngeal microbiota is needed. Dr. Chonmaitree is a pediatric infectious disease physician who has performed extensive research on AOM pathogenesis. Her long-term research goals are to elucidate the contribution of infectious pathogens, and their complex interactions with other otitis risk factors in the pathogenesis of and recovery from AOM, and to identify possible strategies for more effective prevention and treatment. Under the supervision of an experienced mentoring team of expert scientists at the Baylor College of Medicine (BCM) and the University of Texas Medical Branch, the PI will be trained in the novel areas of metagenomics and microbiome, including didactic, laboratory techniques and analyses, with the future goal to independently lead a research program in microbiome of the respiratory tract, in relation to viral URI and AOM. Data will be generated on acquisition of nasopharyngeal microbiota in 150 infants in a Galveston birth cohort; half of whom developed AOM in the first year of life. Specific Aims are to characterize nasopharyngeal microbiota in infants followed from near birth up to 12 months of age and elucidate how changing patterns of nasopharyngeal bacterial colonization in infants lead to susceptibility to viral URI and AOM development. The outstanding metagenomics and microbiome facilities and expertise at the BCM, availability of sequential respiratory specimens from near birth, and the unique and complement environment at the two neighboring institutions will assure the project's success. Better understanding of the respiratory tract microbiota of young infants will facilitate the rationale design of new interventions to reduce colonization of pathogens, such as upper respiratory tract probiotics, or respiratory microbiota transplant, which, in turn, will help minimize the public health burden of AOM and other common childhood respiratory diseases.

描述（由申请人提供）：中耳炎是儿科实践中最常见的疾病之一，也是儿童服用抗生素或接受手术的最常见原因。急性中耳炎（AOM）是一种多种微生物疾病，其发病机制涉及细菌、病毒和宿主炎症反应之间复杂的相互作用。该疾病主要是病毒性上呼吸道感染（URI）的并发症。 AOM 细菌病原体定植于呼吸道，但在发生病毒性 URI 之前不会造成伤害； URI 相关炎症导致咽鼓管功能障碍，从而促进定植的细菌病原体和/或 URI 病毒进入中耳。上呼吸道在出生时是无菌的，但婴儿在生命的最初几个月逐渐获得复杂的细菌群落。数百种不同类型的细菌，包括病原体和共生菌，都可能在上呼吸道定殖。 AOM 细菌病原体的早期定植与早期 AOM 发病以及以后生活中复发性慢性中耳炎密切相关。数据显示鼻咽中定植的细菌病原体之间的相互作用以及病原体和共生定植之间的竞争。预防细菌 AOM 的一种方法是通过增强共生定植来减少病原体定植。为了实现这一目标，需要更好地了解鼻咽微生物群的复杂相互作用。 Chonmaitree 博士是一名儿科传染病医生，对 AOM 发病机制进行了广泛的研究。她的长期研究目标是阐明传染性病原体的作用，以及它们与其他中耳炎危险因素在 AOM 发病机制和恢复中的复杂相互作用，并确定更有效的预防和治疗的可能策略。在贝勒医学院 (BCM) 和德克萨斯大学医学分院经验丰富的专家科学家指导团队的监督下，PI 将接受宏基因组学和微生物组新领域的培训，包括教学、实验室技术和分析，未来的目标是独立领导与病毒 URI 和 AOM 相关的呼吸道微生物组研究项目。将通过采集加尔维斯顿出生队列中 150 名婴儿的鼻咽微生物群来生成数据；其中一半在生命的第一年就出现了 AOM。具体目标是描述婴儿从出生后一直到 12 个月的鼻咽部微生物群特征，并阐明婴儿鼻咽部细菌定植模式的变化如何导致对病毒 URI 和 AOM 发展的易感性。 BCM 出色的宏基因组学和微生物组设施和专业知识、临近出生时的连续呼吸道标本的可用性以及两个相邻机构独特且互补的环境将确保该项目的成功。更好地了解幼儿呼吸道微生物群将有助于合理设计新的干预措施，以减少病原体的定植，例如上呼吸道益生菌或呼吸道微生物移植，这反过来又有助于减轻 AOM 的公共卫生负担和其他常见的儿童呼吸道疾病。