The association between the urine microbiome, the host immune response and urinary symptoms in children with spina bifida

脊柱裂儿童尿液微生物组、宿主免疫反应和泌尿系统症状之间的关系

• 批准号: 10599974
• 负责人: Catherine S Forster
• 金额: $ 18.77万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599974
• 关键词: 16S ribosomal RNA sequencing; Address; Adult; Algorithms; Antibiotic Resistance; Antibiotic Therapy; Antibiotic-resistant organism; Antibiotics; Area; Award; Bacteriuria; Bioinformatics; Biological Markers; Bladder; Bladder Diseases; Bladder Injury; Caring; Cessation of life; Characteristics; Child; Child Health; Childhood; Chronic; Clinical; Clinical Research; Complement; Data; Dedications; Development; Development Plans; Diagnosis; Diagnostic Procedure; Diagnostic tests; Environment; Escherichia coli; Evaluation; Funding; Genetic; Genetic Models; Goals; Health; Health Care Costs; High Prevalence; Hospitals; Immune response; Inflammation; Institution; International; Knowledge; LCN2 gene; Literature; Measures; Medicine; Mentors; Mentorship; Methods; Mission; Modeling; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Neurogenic Bladder; Operative Surgical Procedures; Organism; Outcome; Patients; Pediatric Hospitals; Pediatric cohort; Persons; Population; Probability; Protocols documentation; Publishing; Renal function; Reporting; Research; Research Personnel; Research Training; Resistance; Resources; Risk; Sampling; Spinal Dysraphism; Study models; Symptoms; Testing; Training; Translating; Universities; Urinary tract; Urinary tract infection; Urine; Urodynamics; Uropathogenic E. coli; Urothelium; Work; accurate diagnosis; antimicrobial peptide; biomarker identification; candidate marker; career; career development; clinical training; cohort; cytokine; design; diagnostic algorithm; evidence base; experience; high risk; high risk population; improved; infection risk; innovation; microbial; microbiome; mouse genetics; mouse model; multi-drug resistant pathogen; nonpathogenic Escherichia coli; novel; pediatric patients; pediatrician; preservation; prospective; recruit; skills; urinary; urologic

Catherine Forster, MD, MS is a pediatrician in hospital medicine whose overarching career goal is to be a world-recognized leader on UTIs in children with neuropathic bladder. Research: Despite the importance of urinary tract infections (UTIs) to health outcomes in children with neuropathic bladders, there are currently no methods to accurately diagnose UTIs in this population. This proposal will begin to fill that gap. The goals of this proposal are to identify children who should be tested for a UTI, develop a highly specific diagnostic method for UTI using mouse models, and translate these results into a pilot cohort of children. These goals will be attained through completion of the following specific aims: 1) Develop an algorithm based on clinical characteristics to determine the probability of UTI in children with spina bifida; 2) Identify the relationship between urine microbial diversity and urinary biomarkers in mouse models of neuropathic bladder; and 3) Explore the association between UTI and urobiome diversity and/or urine biomarkers in children with spina bifida. Aim 1 will be completed through use of data from the multi-institutional Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida study. Aim 2 will use both genetic and surgical mouse models of neuropathic bladder. In Aim 3, the urobiome and urine biomarkers will be measured in symptomatic children with spina bifida. Career Development: Together with her mentors, Dr. Carl Bates and Dr. Nader Shaikh, Dr. Forster has created a career development plan built upon her prior training that is designed to address the areas where she requires additional training: Gain additional knowledge around mouse bladder studies and genetic models of bladder disease, create and maintain a mouse colony, gain experience with interpretation of urodynamic data, develop working knowledge of bioinformatic approaches to analyze 16S rRNA sequencing data, and develop expertise with recruiting and collecting prospective urine samples from a cohort of pediatric patients. The proposed training plan will provide Dr. Forster with the necessary skills to validate the results of this work. Environment: This research will take place within the Children’s Hospital of Pittsburgh (CHP). The proposed career development plan utilizes the intellectual resources available through the University of Pittsburgh and CHP, including the Center for Microbiome and Medicine, and nationally recognized seminars and courses. Summary: This proposed innovative research will expand the evidence base for the diagnosis of UTI in children with spina bifida. Aligned with NIDDK’s mission, this work will be an important contribution to improving the health of children with neuropathic bladders. Dr. Forster's research and clinical training, prior research experiences, and dedicated mentorship team make her ideally suited to pursue this research. This award will facilitate Dr. Forster’s continued development into an independent investigator in the conduct of research of the optimizing the care and outcomes of children with neuropathic bladders.

凯瑟琳福斯特，医学博士，MS是在医院医学的儿科医生，其首要的职业目标是成为一个 世界公认的神经性膀胱儿童UTI的领导者。 研究：尽管尿路感染（UTIs）对儿童健康结果的重要性， 对于神经性膀胱，目前没有方法准确诊断该人群中的UTI。这 将开始提出建议来填补这一空白。这项提案的目标是确定哪些儿童应该接受检测， UTI，使用小鼠模型开发UTI的高度特异性诊断方法，并将这些结果转化为 一群试点儿童这些目标将通过完成以下具体目标来实现： 开发一种基于临床特征的算法，以确定脊柱畸形儿童发生UTI的概率 2）确定小鼠模型中尿液微生物多样性和尿液生物标志物之间的关系， 神经性膀胱;和3）探索UTI与尿生物多样性和/或尿液之间的关联 脊柱裂儿童的生物标志物。目标1将通过使用来自多机构 脊柱裂患儿的泌尿系统管理以保持初始肾功能方案研究。 目的2将使用神经性膀胱的遗传和外科小鼠模型。在目标3中，尿生物群系和 将在有症状的脊柱裂儿童中测量尿液生物标志物。 职业发展：福斯特博士与她的导师卡尔·贝茨博士和纳德·沙奎尔博士一起， 根据她之前的培训制定了职业发展计划，旨在解决以下领域： 她需要额外的培训：获得有关小鼠膀胱研究和遗传模型的额外知识 膀胱疾病，建立和维持一个小鼠群体，获得尿动力学解释的经验 数据，发展生物信息学方法的工作知识，以分析16 S rRNA测序数据， 培养从儿科患者队列中招募和收集前瞻性尿液样本的专业知识。 拟议的培训计划将为福斯特博士提供必要的技能，以验证这项工作的结果。 环境：这项研究将在匹兹堡儿童医院（CHP）进行。拟议 职业发展计划利用匹兹堡大学提供的智力资源， 卫生防护中心，包括微生物组和医学中心，以及国家认可的研讨会和课程。 总结：这项拟议的创新研究将扩大泌尿系感染诊断的证据基础， 患有脊柱裂的儿童。与NIDDK的使命一致，这项工作将是对 改善患有神经性膀胱的儿童的健康状况。福斯特博士的研究和临床训练， 研究经验，和专门的导师团队使她非常适合从事这项研究。这 该奖项将促进福斯特博士的继续发展成为一个独立的调查员，在进行 优化神经性膀胱患儿的护理和预后的研究。