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: 10448844
• 负责人: Catherine S Forster
• 金额: $ 18.81万
• 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/10448844
• 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; Cessation of life; Characteristics; Child; Child Health; Childhood; Chiroptera; Chronic; Clinical; Clinical Research; Complement; Data; Development; Development Plans; Diagnosis; Diagnostic Procedure; Diagnostic tests; Environment; Escherichia coli; Evaluation; Funding; Genetic; Genetic Models; Goals; Gold; Health; Health Care Costs; High Prevalence; Hospitals; Immune response; Inflammation; 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; Resistance; Resources; Risk; Sampling; Spinal Dysraphism; Study models; Symptoms; Testing; Training; Translating; Universities; Urinary tract; Urinary tract infection; Urine; Urodynamics; Urothelium; Work; accurate diagnosis; antimicrobial peptide; base; candidate marker; care outcomes; career; career development; 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，医学硕士是医院医学的儿科医生，她的首要职业目标是成为一名儿科医生