Large-scale phage cultivation for commensal human gut bacteria

Phages are highly abundant in the human gut, yet most of them remain uncultured. Here, we present a gut phage isolate collection (GPIC) containing 209 phages for 42 commensal human gut bacterial species. Genome analysis of the phages identified 34 undescribed genera. We discovered 22 phages from the Salasmaviridae family that have small genomes (∼10–20 kbp) and infect Gram-positive bacteria. Two phages from a candidate family, Paboviridae, with high prevalence in the human gut were also identified. Infection assays showed that Bacteroides and Parabacteroides phages are specific to a bacterial species, and strains of the same species also exhibit substantial variations in phage susceptibility. A cocktail of 8 phages with a broad host range for Bacteroides fragilis strains effectively reduced their abundance in complex host-derived communities in vitro. Our study expands the diversity of cultured human gut bacterial phages and provides a valuable resource for human microbiome engineering. [Display omitted] •Large-scale cultivation was used to isolate 209 phages for 42 human gut bacterial species•Genomic analysis reveals isolated phage diversity and discovers two phage families•Bacteroides and Parabacteroides strains show great variations in phage susceptibility•A phage cocktail reduces abundance of the targeted species in communities in vitro Shen et al. isolate and characterize a collection of 209 phages for human gut bacteria. They discover Salasmaviridae phages with small genomes and highly prevalent candidate Paboviridae phages. A phage cocktail reduced abundance of the targeted species in host-derived communities in vitro, suggesting their application in targeting the gut microbiome.