Comparative Metagenomic Analysis of Bacteriophages and Prophages in Gnotobiotic Mouse Models

Gnotobiotic murine models are important to understand microbiota-host interactions. Despite the role of bacteriophages as drivers for microbiome structure and function, there is no information about the structure and function of the gut virome in gnotobiotic models and the link between bacterial and bacteriophage/prophage diversity. We studied the virome of gnotobiotic murine Oligo-MM12 (12 bacterial species) and reduced Altered Schaedler Flora (ASF, three bacterial species). As reference, the virome of Specific Pathogen-Free (SPF) mice was investigated. A metagenomic approach was used to assess prophages and bacteriophages in the guts of 6-week-old female mice. We identified a positive correlation between bacteria diversity, and bacteriophages and prophages. Caudoviricetes (82.4%) were the most prominent class of phages in all samples with differing relative abundance. However, the host specificity of bacteriophages belonging to class Caudoviricetes differed depending on model bacterial diversity. We further studied the role of bacteriophages in horizontal gene transfer and microbial adaptation to the host's environment. Analysis of mobile genetic elements showed the contribution of bacteriophages to the adaptation of bacterial amino acid metabolism. Overall, our results implicate virome "dark matter" and interactions with the host system as factors for microbial community structure and function which determine host health. Taking the importance of the virome in the microbiome diversity and horizontal gene transfer, reductions in the virome might be an important factor driving losses of microbial biodiversity and the subsequent dysbiosis of the gut microbiome.