A catalog of tens of thousands of viruses from human metagenomes reveals hidden associations with chronic diseases

Significance Mechanisms of many human chronic diseases involve abnormal action of the immune system and/or altered metabolism. The microbiome, an important regulator of metabolic and immune-related phenotypes, has been shown to be associated with or participate in the development of a variety of chronic diseases. Viruses of bacteria (i.e., “phages”) are ubiquitous and mysterious, and several studies have shown that phages exert great control over the behavior—and misbehavior—of their host bacteria. This study uses techniques to discover and analyze over 45,000 viruses associated with human bodies. The abundance of over 2,000 specific phages is found to correlate with a variety of common chronic diseases.
Despite remarkable strides in microbiome research, the viral component of the microbiome has generally presented a more challenging target than the bacteriome. This gap persists, even though many thousands of shotgun sequencing runs from human metagenomic samples exist in public databases, and all of them encompass large amounts of viral sequence data. The lack of a comprehensive database for human-associated viruses has historically stymied efforts to interrogate the impact of the virome on human health. This study probes thousands of datasets to uncover sequences from over 45,000 unique virus taxa, with historically high per-genome completeness. Large publicly available case-control studies are reanalyzed, and over 2,200 strong virus–disease associations are found.