2023 FDA Science Forum
The impact of various routes of administered phages on host microbial community
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Contributing OfficeCenter for Biologics Evaluation and Research
Abstract
Antimicrobial resistance (AMR) is a growing global health threat that necessitates the development of alternative treatments beyond the currently available antimicrobials. Bacteriophage (“phage”) therapy is a promising biotherapeutic that has seen renewed interest in recent years. Unlike broad-spectrum antibiotics, phage typically target only a single bacterial species or strain. Due to this specificity, there is a general assumption in the field that bacteriophage therapy will have minimal impacts on the host microbiome. However, few studies have thoroughly assessed changes in microbial community composition in a host following phage administration. To fully evaluate this therapeutic modality, it is important to understand the potential effect of phage on non-target species and the overall composition of the gut microbiome. To investigate this, we developed a murine model and bioinformatics pipeline to explore the diversity metrics and to characterize the composition of microbial communities following administration of a cocktail of phages. We have previously shown efficacy of a phage cocktail in reducing the numbers of vancomycin-resistant enterococcus (VRE) in the gastrointestinal tract. Through analyzing fecal pellets, the bacterial burden of VRE was shown to be significantly reduced with administration of the phage cocktail using intraperitoneal (IP) injection. We will examine the bacterial composition of the microbiome by isolating and sequencing the V4 variable region on the 16S rRNA gene, which is conserved across all bacterial species. We will explore differences between administration routes for phage therapy, including intravenous (IV) injection and oral gavage, and their effect on the composition and diversity of the murine intestinal microbiome. Observations of microbiome disruption following administration of phage will be followed additional experimentation to attempt to elucidate interactions between the treatment and the microbial community. Observations of no significant perturbation in the intestinal microbiome with administration of phage will be confirmed through sampling and repetition to support conclusions. This investigation in total will support further development and understanding of phage therapy and the interactions between the phage, the host, and the host microbiota
