Respiratory Tract Microbiota and Acute Otitis Media Development in Young Infants

描述(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。该病大多发生为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发生之前不会造成损害；URI相关的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，但婴儿在出生后的头几个月逐渐形成复杂的细菌群落。数百种不同类型的细菌，包括病原体和共生体，可能会在上呼吸道定居。AOM细菌病原体的早期定植与AOM的早期发病以及晚年复发和慢性中耳炎密切相关。数据表明，定植细菌病原体之间的相互作用，以及病原体与鼻咽共生定植之间的竞争。预防细菌性AOM的方法之一是通过加强共生定植来减少病原菌定植。为了实现这一目标，需要更好地了解鼻咽微生物区系的复杂相互作用。Chonmaitree博士是一位儿科传染病内科医生，他对AOM的发病机制进行了广泛的研究。她的长期研究目标是阐明感染性病原体的作用，以及它们与其他中耳炎危险因素在AOM的发病和康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院分校经验丰富的专家科学家指导团队的监督下，PI将接受元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有关的呼吸道微生物组的研究计划。将生成关于加尔维斯顿出生队列中150名婴儿鼻咽微生物区系获取的数据；其中一半婴儿在出生第一年就患上了AOM。具体目的是描述从近出生到12个月大的婴儿鼻咽微生物区系的特征，并阐明婴儿鼻咽细菌定植模式的变化如何导致对病毒性URI和AOM的易感性。BCM出色的元基因组和微生物组设施和专业知识、近生婴儿的连续呼吸道样本的可获得性，以及邻近两个机构独特和互补的环境将确保项目的成功。更好地了解婴幼儿的呼吸道微生物区系将有助于设计新的干预措施的基本原理，以减少病原体的定植，如上呼吸道益生菌或呼吸道微生物区系移植，这反过来将有助于将AOM和其他常见儿童呼吸道疾病的公共卫生负担降至最低。

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.