Cosmopolitan gut bacteriophages expand the phenotype of health-related bacteria

Metagenomics has vastly expanded our knowledge of the human gut virome, yet the focus on dominant taxa has missed low-abundant but highly prevalent bacteriophages. Here, high-sensitivity taxonomic profiling of 53,976 samples from 42 countries, including non-industrialised populations and ancient DNA from five archaeological sites, reveals that only 0.3% of 64,238 phage genera are cosmopolitan, occurring in >20% of all subjects and on six continents. The most prevalent of these is Mushuvirus, with two distinct species detected in 60% of individuals, previously missed due to artefacts in reference genomes and their consistently low relative abundance (<0.8%). Population genomics shows that while one species is globally ubiquitous, the other predominates in individuals with West Eurasian ancestry. Together with 12 additional novel genera, we propose to classify these viruses into a new family Mushuviridae, found in [~]89% of studied humans. These transposable phages integrate into diverse hosts from two taxonomic orders of short-chain fatty acid-producing bacteria. Multi-omics experiments with Faecalibacterium demonstrate that hosts produce and secrete Mushuvirus-encoded receptor-binding proteins, which are actively diversified in lysogenic hosts. Together, these findings illuminate a globally distributed, active phage lineage that has persisted for millennia and continues to reshape the functional repertoire of bacteria central to human gut health.