Research Project
10283837
Project Summary/Abstract The gastrointestinal tract of preterm infants plays a major role in overall infant nutrition, growth, and health. Increasing interest by clinicians and researchers has uncovered relationships between the gut microbiome and many of the primary causes of morbidity and mortality in preterm infants. To address these risks from the gut microbiome, probiotics are an attractive and translatable approach to remodel the infant gut microbiome. However, there is a strong need to understand the mechanism by which probiotic organisms act on the preterm gut and with the gut ecosystem in order to guide the rational selection of probiotic organisms for use in this patient population. In particular, there is a current lack of understanding as to how genomic variation among probiotic organisms may, or may not, influence their relative efficacy and/or safety in vivo. The proposed studies begin to address these issues by (1) examining the impact of genomic variations within a well characterized infant gut symbiont, and frequent probiotic organism, B. infantis, on ecological performance in in vitro competition models and then (2) how these variations affect the preterm gut epithelium in an epithelial cell line that closely mimics the cells found in the preterm infant gut. Together, these experiments seek to understand how diet (i.e. human milk), a probiotic gut symbiont (B. infantis), and the preterm host interact in terms of both transcriptional responses and host immune, proliferative, and necroptotic responses.
