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 Salas-maviridae 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 com-munities in vitro. Our study expands the diversity of cultured human gut bacterial phages and provides a valu-able resource for human microbiome engineering.

Automated summary

In this study, a collection of 209 gut phages for 42 commensal human gut bacterial species was presented and analyzed. Genome analysis revealed 34 previously undescribed genera of phages. The study also identified two phages from a candidate family, Paboviridae, that were highly prevalent in the human gut. Infection assays demonstrated the specificity of Bacteroides and Parabacteroides phages to bacterial species, as well as substantial variations in phage susceptibility among strains of the same species. Furthermore, a cocktail of 8 phages effectively reduced the abundance of Bacteroides fragilis strains in vitro. This study expands the diversity of cultured human gut bacterial phages and provides a valuable resource for human microbiome engineering.