Research Project
10127219
Project Summary/Abstract Evidence of the long-term detriment to humans following early life malnutrition is compelling, but to develop interventions to help these individuals we need to uncover the mechanisms responsible for impairment. A key gap in the literature relates to the microbiome and metabolome of growth restricted individuals. We have previously collected fecal samples and tissue samples ready to be analyzed to fill this gap in the literature. Thus, this application fits the scope of the Eunice Kennedy Shriver National Institute of Child Health and Development to promote health across the lifespan. Furthermore, this application aligns with one of the goals of NIH to integrate ?omic? datasets. Our long-term goal is to develop therapeutic countermeasures to restore health following growth restriction. In order to take the first step towards completing our long-term goal we will test the hypothesis: The Gut-Liver metabolic axis is disrupted in growth restricted mice due to changes in host microbiota and bile acid metabolism which contributes to the development of chronic disease through disruption of early nutrient adsorption leading to functional impairment. We will evaluate this hypotheses with the following aims: Aim 1: Determine the microbial and metabolite variation and associated liver metabolism in growth restricted mice from birth to adulthood compared to healthy controls. Aim 2: Determine the effects of growth restriction on bile acid synthesis and organ growth. We have assembled a collaborative research team experienced in the proposed techniques and have already collected samples that are ready for analysis. Therefore, there is a high likelihood of successfully completing this project in the allotted timeframe. We will determine causal relationships between the gut microbiome and metabolome allowing for future targeted interventions to restore functional capacity in the growth restricted population. Following this we are poised to seek R01 funding to evaluate the therapeutic countermeasures for the mechanisms determined in this application.
