Grant Abstract: Gut microflora: Impact on neonatal immunity, viral gastroenteritis, and vaccines

Grant Number: 5R01AI099451-05
PI Name: Saif
Project Title: Gut microflora: Impact on neonatal immunity, viral gastroenteritis, and vaccines

Abstract: The purpose of this supplement request is to support a complementary and newly developed improved approach to the ongoing studies in our original R01 AI099451 (Title: Gut microflora: Impact on neonatal immunity, viral gastroenteritis and vaccines) by testing a novel probiotic delivery system to prolong the persistence of probiotics in the gut and to enhance their beneficial effects. Our hypothesis is that oral administration of probiotics (L. reuteri and E. coli Nissle 1917) in a biofilm state attached to the surface of biocompatible microspheres with beneficial cargo will persist in the gut and enhance their beneficial effects after a single administration. In our current R01, we are testing the impact of Gram positive (G+) and Gram negative (G-) probiotic bacteria in gnotobiotic (Gn) pigs and Gn pigs colonized with defined microflora (DMF; 8 known species) in a human rotavirus (HRV) disease model. Although the DMF-HRV model better mimics the infant gut microflora than the Gn model, it still does not completely reflect the microbial complexity of an infant gut. Therefore, we will test the probiotic bacteria using a microflora humanized Gn pig model (Gn pigs colonized with infant gut microflora, HMF). We will administer these probiotics as biofilms attached to microspheres that will give a competitive advantage for the probiotic bacteria to successfully colonize or establish itself for a prolonged period in the gut. This approach should provide superior, longer lasting beneficial effects compared to the current practice of repetitive administration of probiotics in the suspension form, which results in transient and often inconsistent outcomes. Our approach will serve as a pilot study, and if successful, it will significantly impact treatment/control of enteric infections and disorders including chronic disorders such as Inflammatory Bowel Disease (IBD) through dietary supplementation of probiotics. It is highly relevant to the goals of the RFA including discovery of dietary supplements to reduce the risk for chronic conditions and as an administrative supplement to enhance our research on probiotics to prevent viral diarrheas and stimulate neonatal immunity.

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