Discovery, diversity, and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts

The crAss-like phages are a diverse group of related viruses that includes some of the most abundant viruses of the human gut. To explore their diversity and functional role in human population and clinical cohorts, we analyze gut metagenomic data collected from 1,950 individuals from the Netherlands. We identify 1,556 crAss-like phage genomes, including 125 species-level and 32 genus-level clusters absent from the reference databases used. Analysis of their genomic features shows that closely related crAss-like phages can possess strikingly divergent regions responsible for transcription, presumably acquired through recombination. Prediction of crAss-like phage hosts points primarily to bacteria of the phylum Bacteroidetes, consistent with previous reports. Finally, we explore the temporal stability of crAss-like phages over a 4-year period and identify associations between the abundance of crAss-like phages and several human phenotypes, including depletion of crAss-like phages in inflammatory bowel disease patients.