SBIR-STTR Award

Diarrhea remains a major public health challenge worldwide, and it also may significantly hamper US troop operations during combat and peacekeeping missions overseas. Antibiotics can be used to treat diarrheal diseases; however, some foodborne and waterborne bacterial pathogens are developing resistance against antibiotics, which limits their effectiveness. Also, antibiotics – because of their broad spectrum activity – may disturb/alter the GI tract’s normal and beneficial microflora, which may create additional health problems. Therefore, novel approaches are needed to help prevent and treat bacterial-elicited diarrhea among US troops, thereby improving their combat readiness and performance. Synbiotics (combinations of probiotics and prebiotics) may provide one such approach. However, one potentially useful probiotic intervention that has not received much attention in the past is to use bacteriophages to target “problem” bacterial species in the human GI tract. Bacteriophages are viruses that infect bacteria, are highly specific, and lyse their targeted bacteria, including antibiotic-resistant strains. Thus, synbiotic preparations containing (i) bacteriophages targeting specific diarrhea-causing bacteria, (ii) previously described, bacteria-based probiotics, and (iii) prebiotics may provide excellent protection against diarrheal illnesses among US troops and civilian populations. In this application, we propose to begin developing and testing a synbiotic preparation whose phage component is specifically active against Shigella spp., which are significant diarrhea-causing pathogens.

Keywords:
Bacteriophages, Phages, Probiotics, Synbiotics, Dietary Supplements, Shigella

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.

Keywords:
Bacteriophages, Phages, Probiotics, Shigella, Diarrheal Illness