Often physiological studies using mice from one vendor show different outcome when being reproduced using mice from another vendor. These divergent phenotypes between similar mouse strains from different vendors have been assigned to differences in the gut microbiome. During recent years, evidence has mounted that the gut viral community plays a key role in shaping the gut microbiome and may thus also influence mouse phenotype. However, to date inter-vendor variation in the murine gut virome has not been studied. Using a metavirome approach, combined with 16S rRNA gene sequencing, we here compare the composition of the viral and bacterial gut community of C57BL/6N mice from three different vendors exposed to either a chow-based low-fat diet or high-fat diet. Interestingly, both the bacterial and the viral component of the gut community differed significantly between vendors. The different diets also strongly influenced both the viral and bacterial gut community, but surprisingly the effect of vendor exceeded the effect of diet. In conclusion, the vendor effect is substantial not only on the gut bacterial community but also strongly influences viral community composition. Given the effect of GM on mice phenotype, this is essential to consider for increasing reproducibility of mouse studies.

Often physiological studiess using mice from one vendor show different outcome when being 16 reproduced using mice from another vendor. These divergent phenotypes between similar mouse strains 17 from different vendors have been assigned to differences in the gut microbiome. During recent years, 18 evidence has mounted that the gut viral community plays a key role in shaping the gut microbiome and may 19 thus also influence mouse phenotype. However, to date inter-vendor variation in the murine gut virome has 20 not been studied. Using a metavirome approach, combined with 16S rRNA gene sequencing, we here 21 compare the composition of the viral and bacterial gut community of C57BL/6N mice from three different 22 vendors exposed to either a chow-based low-fat diet or high-fat diet. Interestingly, both the bacterial and the 23 viral component of the gut community differed significantly between vendors. The different diets also 24 strongly influenced both the viral and bacterial gut community, but surprisingly the effect of vendor 25 exceeded the effect of diet. In conclusion, the vendor effect is substantial on not only the gut bacterial 26 community, but also strongly influences viral community composition. Given the effect of GM on mice 27 phenotype this is essential to consider, for increasing reproducibility of mouse studies. 28 29