Respiratory Tract Microbiota and Acute Otitis Media Development in Young Infants

项目总结/摘要 中耳炎是儿科最常见的疾病之一， 儿童服用抗生素或接受手术。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的复杂相互作用。 这种疾病主要是病毒性上呼吸道感染（URI）的并发症。AOM细菌 病原体在呼吸道定植，但在病毒性URI发生之前不会造成伤害; URI相关炎症 导致咽鼓管功能障碍，这有助于定植的细菌病原体的进入，和/或 URI病毒进入中耳。上呼吸道在出生时是无菌的，但婴儿逐渐获得 复杂的细菌群落。数百种不同类型的细菌， 病原体和细菌，可能潜在地在上呼吸道定植。AOM早期定殖 细菌性病原体与早期AOM发作和以后生活中的复发性和慢性耳炎高度相关。数据 已经显示了定殖细菌病原体之间的相互作用以及病原体和 鼻咽部的细菌定植。预防细菌性AOM的一种方法是减少病原体 通过加强殖民地化。为了达到这一目标，更好地了解复杂的 需要鼻咽微生物群的相互作用。Chonmaitree医生是一种儿科传染病 对AOM发病机制进行了广泛研究的医生。她的长期研究目标是 阐明感染性病原体的贡献，以及它们与其他中耳炎危险因素的复杂相互作用， AOM的发病机制和恢复，并确定更有效预防的可能策略 和治疗。在贝勒大学经验丰富的专家科学家指导团队的监督下， 医学院（马里兰大学）和得克萨斯大学医学分支，PI将在小说中进行培训 宏基因组学和微生物组学领域，包括教学、实验室技术和分析， 我的目标是独立领导一个与病毒URI相关的呼吸道微生物组研究项目 和AOM。将在加尔维斯顿的150名婴儿中采集鼻咽微生物群数据 出生队列;其中一半在出生后第一年发生AOM。具体目标是描述 婴儿鼻咽部微生物群从出生到12个月大， 婴儿鼻咽部细菌定植模式的改变导致对病毒性URI的易感性， AOM开发。杰出的宏基因组学和微生物组学设施和专业知识， 从近出生开始的连续呼吸道标本的可用性，以及独特和互补的环境 将确保该项目的成功。更好地了解呼吸系统 婴幼儿肠道微生物群将促进新干预措施的合理设计，以减少 病原体，如上呼吸道益生菌，或呼吸道微生物群移植，这反过来，将 有助减低急性有机污染物及其他常见儿童呼吸道疾病对公众健康造成的负担。

PROJECT SUMMARY/ ABSTRACT 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.