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.

Catherine Forster，医学博士、理学硕士是一名医院医学儿科医生，其首要职业目标是成为一名 世界公认的神经性膀胱儿童尿路感染领域的领导者。 研究：尽管尿路感染 (UTI) 对患有尿路感染的儿童的健康结果很重要， 神经性膀胱，目前没有方法可以准确诊断该人群的尿路感染。 该提案将开始填补这一空白。该提案的目标是确定应该接受检测的儿童。 UTI，使用小鼠模型开发一种高度特异性的 UTI 诊断方法，并将这些结果转化为 这些目标将通过完成以下具体目标来实现：1) 开发一种基于临床特征的算法来确定脊柱儿童尿路感染的概率 2) 鉴定小鼠模型中尿液微生物多样性与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将通过使用多机构的数据来完成。 泌尿系统管理以保留脊柱裂幼儿的初始肾功能方案研究。 目标 2 将使用神经性膀胱的遗传和手术小鼠模型。目标 3 将使用尿生物组和神经性膀胱模型。 将测量有脊柱裂症状的儿童的尿液生物标志物。 职业发展：福斯特博士与她的导师 Carl Bates 博士和 Nader Shaikh 博士一起， 根据她之前的培训制定了职业发展计划，旨在解决以下领域的问题： 她需要额外的培训：获得有关小鼠膀胱研究和遗传模型的更多知识 膀胱疾病，创建和维持小鼠群体，获得解释尿动力学的经验 数据，发展生物信息学方法的工作知识来分析 16S rRNA 测序数据，以及 培养从儿科患者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验证这项工作结果所需的技能。 环境：这项研究将在匹兹堡儿童医院 (CHP) 内进行。 职业发展计划利用匹兹堡大学提供的智力资源和 CHP，包括微生物组和医学中心，以及国家认可的研讨会和课程。 摘要：这项拟议的创新研究将扩大尿路感染诊断的证据基础 这项工作符合 NIDDK 的使命，将为患有脊柱裂的儿童做出重要贡献。 改善患有神经性膀胱的儿童的健康，之前福斯特博士的研究和临床培训。 研究经验和敬业的导师团队使她非常适合从事这项研究。 该奖项将促进福斯特博士继续发展成为一名独立调查员，从事以下研究 优化神经病性膀胱儿童的护理和结果的研究。