Bacteriophage administration significantly reduces<i>Shigella</i>colonization and shedding by<i>Shigella</i>-challenged mice without deleterious side effects and distortions in the gut microbiota

Abstract

We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecal <i>Shigella</i> counts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged with <i>Shigella sonnei</i> strain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lytic <i>Shigella</i> bacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActive ^<b>TM</b> treatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration. <i>Shigella</i> phages may be therapeutically effective in a "classical phage therapy" approach, at least during the early stages after <i>Shigella</i> ingestion. Oral prophylactic "phagebiotic" administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota.