Highlights d The human gut virome is highly individual and stable for up to 1 year d A stable and predominant fraction of viruses constitutes a persistent personal virome d Persistent bacteriophages can be linked to highly predominant gut bacterial taxa d Virulent crAss-like and Microviridae bacteriophages predominate and persist in the gut

CrAssphages are an extensive and ubiquitous family of tailed bacteriophages, predicted to infect bacteria of the order Bacteroidales. Despite being found in ~50% of individuals and representing up to 90% of human gut viromes, members of this viral family have never been isolated in culture and remain understudied. Here, we report the isolation of a CrAssphage (ΦCrAss001) from human faecal material. This bacteriophage infects the human gut symbiont Bacteroides intestinalis, confirming previous in silico predictions of the likely host. DNA sequencing demonstrates that the bacteriophage genome is circular, 102 kb in size, and has unusual structural traits. In addition, electron microscopy confirms that ΦcrAss001 has a podovirus-like morphology. Despite the absence of obvious lysogeny genes, ΦcrAss001 replicates in a way that does not disrupt proliferation of the host bacterium, and is able to maintain itself in continuous host culture during several weeks.

SummaryThe human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterised and their roles in shaping the gut microbiome and in impacting on human health remain poorly understood. Here we performed a longitudinal focused metagenomic study of faecal bacteriophage populations in healthy adults. Our results reveal high temporal stability and individual specificity of bacteriophage consortia which correlates with the bacterial microbiome. We report the existence of a stable, numerically predominant individual-specific persistent personal virome. Clustering of bacteriophage genomes and de novo taxonomic annotation identified several groups of crAss-like and Microviridae bacteriophages as the most stable colonizers of the human gut. CRISPR-based host prediction highlighted connections between these stable viral communities and highly predominant gut bacterial taxa such as Bacteroides, Prevotella and Faecalibacterium. This study provides insights into the structure of the human gut virome and serves as an important baseline for hypothesis-driven research.