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.
The goal of the project is to evaluate the safety and efficacy of the probiotic organism L. reuteri DSM 17938 for the treatment of diarrhea in children in the developing world, a setting where diarrhea and chronic malnutrition are common. The project aims to determine if treatment of diarrhea with probiotics shortens the duration of illness, whether the efficacy varies according to the etiology of the diarrhea, if giving treatment for each episode has a cumulative beneficial impact on the health of the child, and if these effects are mediated through intestinal inflammation and permeability or through structural changes in the population of bacteria inhabiting the gut.
| Kosek, Margaret N; Peñataro-Yori, Pablo; Paredes-Olortegui, Maribel et al. (2018) Safety of Lactobacillus reuteri DSM 17938 in Healthy Children 2 to 5 Years of Age. Pediatr Infect Dis J : |
