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）：中耳炎是小儿实践中最常见的疾病之一，儿童最常见的原因是食用抗生素或接受手术。急性中耳炎培养基（AOM）是一种多性疾病，其发病机理涉及细菌，病毒和宿主炎症反应之间的复杂相互作用。该疾病主要是病毒上呼吸道感染（URI）的并发症。 AOM细菌病原体定居呼吸道，但在病毒URI发生之前不受伤害。尿液相关的炎症会导致尤斯塔克式管功能障碍，这促进了殖民细菌病原体和/或URI病毒进入中耳。出生时，上呼吸道是无菌的，但婴儿在生命的头几个月中逐渐获得复杂的细菌群落。几百种不同类型的细菌，包括病原体和共生，可能会定植上呼吸道。用AOM细菌病原体的早期定殖与早期的早期AOM发作以及早期的慢性中炎高度相关。数据表明，鼻咽病原体和共生定植之间的定殖细菌病原体和竞争之间的相互作用。预防细菌AOM的一种方法是通过增强共生定殖来减少病原体定植。为了实现这一目标，需要更好地了解鼻咽菌群的复杂相互作用。 Chonmaitree博士是一名儿科传染病医师，对AOM发病机理进行了广泛的研究。她的长期研究目标是阐明感染性病原体的贡献，以及它们与其他AOM发病机理和恢复的其他中耳炎风险因素的复杂相互作用，并确定可能进行更有效的预防和治疗的策略。在贝勒医学院（BCM）和德克萨斯大学医学分公司的一支经验丰富的专家科学家团队的监督下，PI将在元基因组学和微生物组的新颖领域进行培训，包括教学，实验室技术和分析，并以未来的目标在呼吸道和OPIRIATION TRACTIRATION IRIAME和OPIRATION IRIAME和OPIRATION INRIATION和ARIAS中独立领导。将生成有关在加尔维斯顿出生队列中150名婴儿中鼻咽微生物群获取的数据；其中一半在生命的第一年发展。具体目的是表征婴儿的鼻咽微生物群，随后近期出生到12个月大，并阐明婴儿鼻咽细菌定植的变化如何导致病毒URI和AOM发育的敏感性。 BCM的杰出宏基因组学和微生物组的设施以及专业知识，临近出生的顺序呼吸标本以及两个邻近机构的独特和补充环境将确保该项目的成功。更好地了解年轻婴儿的呼吸道菌群将有助于促进新干预措施的理由设计，以减少病原体的定殖，例如上呼吸道益生菌或呼吸道菌群移植，从而有助于最大程度地减少AOM和其他常见的儿童呼吸呼吸疾病负担。