A genomic catalog of the mouse gut virome reveals features associated with ageing

Abstract

Abstract The gut virome is emerging as a key contributor to host physiology, yet it remains underexplored relative to the gut bacteriome. Despite comprehensive viral catalogs for the human gut, comparable resources for mice, the principal model organism in biomedical research, remain lacking, limiting our understanding of virome-host interactions and their implications for host health and disease. Here, we present Mouse Reference Gut Virome (MRGV), a comprehensive catalog comprising 109,778 viral genomes with ≥50% completeness and representing 28,824 species, expanding known mouse gut viral diversity by ~67.6%. Viral genome binning accounted for ~36% of cataloged genomes and improved average completeness by ~60% relative to contig-level assemblies. Structure-based annotation assigned functions to nearly half of 8.2 million viral proteins. Comparison with human gut virome revealed pronounced taxonomic and functional divergence. MRGV enabled host linkage for 88% of viral genomes and validated diverse mouse-associated crAss-like lineages with lineage-specific host-range and lifestyle strategies. Finally, mouse gut virome features harbored host ageing-associated signals distinct from those captured by bacterial features, with most ageing markers derived from binned genomes, highlighting the importance of viral binning for elucidating virome-host interactions.