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

描述(申请人提供)：尽管绝大多数腹泻病例发生在生活在贫困环境中的儿童中，但益生菌的安全性和有效性的证据主要来自美国和欧洲。长期目标是提高有关益生菌治疗儿童早期腹泻的安全性、有效性和作用机制的证据质量，以期在生活在极端贫困中的人群中治疗腹泻，那里腹泻、肠病和发育迟缓很常见，因此可以设计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第一阶段研究，然后在秘鲁的一个出生队列中进行第二阶段临床试验来进行。 这些研究的成功完成将评估该人群的安全性，并提供关于路氏乳杆菌DSM 17938对所有原因的腹泻和由诺如病毒、弯曲杆菌、贾第虫和产肠毒素大肠杆菌引起的腹泻的疗效的信息。创新方面包括允许对产品管理的累积效果进行评估的设计 在生命的头两年中，每一次突发事件的压力对疾病的累积负担和线性增长。包括肠道炎症、通透性和全身炎症在内的综合措施将通过对样本亚组的肠道微生物群的研究来补充，以提供有关宿主生理和微生物区系变化的重要新信息，这些变化可能与路支杆菌DSM 17938的治疗相关。研究团队由具有不同背景和丰富经验的科学家组成，他们在临床试验、具有密集监测的纵向实地研究以及北京大学的肠道疾病方面具有丰富的经验，能够很好地实施本提案中描述的监管、现场和基础科学项目组成部分。

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.