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

描述（由申请人提供）：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。长期目标是提高关于益生菌治疗极端贫困人群中幼儿腹泻的安全性，有效性和作用机制的证据质量，腹泻，肠病和发育迟缓是常见的，因此可以设计基于证据的益生菌策略。方法：这项工作将首先在婴儿中进行I期研究，然后在秘鲁的出生队列中进行II期临床试验。 这些研究的成功完成将评估该人群的安全性，并获得关于L. reuteri DSM 17938用于所有原因的腹泻和由诺如病毒、弯曲杆菌、贾第虫和肠出血性大肠杆菌引起的腹泻。杆菌创新方面包括一个设计，允许评估的累积效应的管理的产品 在生命的头两年，每次发病对疾病累积负担和线性增长的压力。包括肠道炎症，渗透性和全身性炎症在内的综合措施将通过对样本子集的肠道微生物组的研究来补充，以提供有关宿主生理学和微生物群变化的重要新信息，这些变化可能与L治疗相关。reuteri DSM 17938.该研究小组由具有不同背景和丰富临床试验经验的科学家组成，纵向实地研究与密集监测，以及Peu的肠道疾病，能够很好地开展本提案中描述的监管，实地和基础科学项目。

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.