Bacteriophage-based probiotic preparation for managing Shigella infections

During the studies supported by our Phase I STTR grant from the US Army, we began developing and testing a novel concept for a probiotic preparation based on naturally occurring bacteriophages as a way to condition the GI tract"s microflora gently and favorably. The preparation (tentatively designated"ShigActive") is a bacteriophage cocktail that specifically targets Shigella spp. (significant diarrhea-causing pathogens that sicken ca. 165 million people/year, ca. 1.1 million of whom die). We have succesfully isolated and rigorously characterized a large number of phages lytic for Shigella, and we have developed a murine model in which the in vivo efficacy of our phage preparation can be evaluated. During this Phase II project, we propose to perform studies required to obtain regulatory approval of ShigActive. During these studies, we will also perform metagenomic analyses of the gut microbiota (using DGGE and state-of-the-art 454-pyrosequencing of 16S rRNA genes) of mice before and after their treatment with ShigActive, in order to (i) obtain additional safety data for the FDA, and (ii) compare rigorously the effect of ShigActive and ampicillin (an antibiotic commonly used to treat shigellosis) on the intestinal microflora of mice. The proposed project"s primary goal is to submit a New Dietary Ingredient (NDI) Notification to the FDA, whose approval will enable us to commence commercial sales of ShigActive.