L. reuteri for Pediatric Diarrhea in Peru: Growth, Enteropathy, and Microbiota

秘鲁治疗小儿腹泻的罗伊氏乳杆菌：生长、肠病和微生物群

• 批准号: 8801071
• 负责人: RICHARD A OBERHELMAN
• 金额: $ 67.54万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-25 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8801071
• 关键词: Acute; Address; Adult; Attenuated; Bacteria; Basic Science; Biological Markers; Birth; Campylobacter; Child; Child health care; Childhood; Chronic; Clinical; Clinical Trials; Communities; Complement; Data; Developing Countries; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Diarrhea; Disease; Double-Blind Method; Ensure; Enteral; Escherichia coli; Etiology; Europe; Evaluation; Failure; Feces; Giardia; Goals; Growth; Guidelines; Incidence; Infant; Infection; Inflammation; Inflammatory disease of the intestine; Intervention; Intestines; Investigation; Laboratories; Lactobacillus reuteri; Life; Malnutrition; Measures; Mediating; Native-Born; Norovirus; Organism; Permeability; Peru; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Physiology; Population; Positioning Attribute; Poverty; Prevalence; Probiotics; Public Health; Randomized; Research; Research Infrastructure; Safety; Sampling; Scientist; Site; Target Populations; United States National Institutes of Health; Work; Zinc; aged; base; burden of illness; cohort; design; early childhood; enterotoxigenic Escherichia coli; evidence base; experience; field study; high risk; improved; innovation; microbial; microbiome; phase 1 study; public health relevance

DESCRIPTION (provided by applicant): Despite the fact that the great majority of cases of diarrhea occur in children living in impoverished settings, the evidence for the safety and efficacy of probiotics is principally derived from the U.S. and Europe. The long term goal is to improve quality of evidence regarding the safety, efficacy, and mechanism of action of probiotics for the treatment of diarrhea in early childhood in a population living in extreme poverty, where diarrhea, enteropathy, and stunting are common, so that evidenced-based probiotic strategies may be designed. Approach: The work will be conducted through first performing a Phase 1 study in infants and then proceeding to conduct a Phase 2 Clinical Trial in a birth cohort in Peru. The successful completion of these studies will evaluate safety in this population and yield information on the efficacy of L. reuteri DSM 17938 for all cause diarrhea and diarrhea caused by Norovirus, Campylobacter, Giardia, and Enteroggerative E. coli. Innovative aspects include a design that allows for the evaluation of the cumulative effect of the administration of the product strain on each incident episode over the first two years of life on the cumulative burden of disease and linear growth. Integrated measures including intestinal inflammation, permeability, and systemic inflammation will be complemented by studies of the gut microbiome on sample subsets to contribute important new information on the changes in the host physiology and microbiota that can be associated with treatment with treatment with L. reuteri DSM 17938. The research team is composed of scientists with diverse backgrounds and extensive experience in clinical trials, longitudinal field studies with intensive surveillance, and enteric diseases in Peu that is well positioned to carry out the regulatory, field, and basic science project components described in this proposal.

描述（由申请人提供）：尽管大部分腹泻病例都发生在贫困环境中的儿童中，但益生菌的安全性和功效的证据主要来自美国和欧洲。长期的目标是提高有关益生菌在幼儿期治疗腹泻的安全性，有效性和作用机制的证据质量，而生活在极端贫困中的人群中，腹泻，肠胃病和发育迟缓是常见的，因此可以设计出基于证据的益生菌策略。方法：这项工作将通过首先在婴儿中进行1期研究，然后在秘鲁的出生队列中进行2期临床试验。 这些研究的成功完成将评估该人群的安全，并产生有关R. Reuteri DSM 17938对所有原因腹泻和腹泻的功效的信息，由诺如病毒，弯曲杆菌，吉亚迪和肠胃腹泻引起。创新方面包括一个设计，该设计允许评估产品的累积效应 在生命的头两年中，每个事件发作都会承受疾病和线性生长的累积负担。通过对样本子集的肠道微生物组进行研究，将补充包括肠道炎症，渗透性和全身性炎症在内的综合措施，以补充有关宿主生理学和微生物群的变化的重要新信息，这些信息可以与L. Reuteri DSM 17938相关的经验研究，这些研究与研究团队进行了多样的经验。 PEU中的监视和肠道疾病，可以很好地执行本提案中描述的监管，领域和基础科学项目组成部分。