A universe of human gut-derived bacterial prophages: unveiling the hidden viral players in intestinal microecology.

Prophages, which are an existing form of temperate phages that integrate into host genomes, have been found extensively present in diverse bacterial species. The human gut microbiome, characterized by its complexity, dynamism, and interconnectivity among multiple species, remains inadequately understood in terms of the global landscape of bacterial prophages. Here, we analyzed 43,942 human gut-derived bacterial genomes (439 species of 12 phyla) and identified 105,613 prophage regions in ~ 92% of them. 16254 complete prophages were distributed in ~ 24% of bacteria, indicating an extremely uneven prophage distribution across various species within the human gut. Among all identified prophages, ~4% possessed cross-genera (2-20 genera) integration capacity, while ~ 17% displayed broad infection host ranges (targeting 2-35 genera). Functional gene annotation revealed that antibiotic-resistance genes and toxin-related genes were detected in ~ 2.5% and ~ 5.8% of all prophages, respectively. Furthermore, through sequence alignments between our obtained prophages and publicly available human gut phageome contigs, we have observed that ~ 72% of non-redundant prophages are previously unreported genomes, and they illuminate ~ 6.5-9.5% of the individual intestinal "viral dark matter". Our study represents the first comprehensive depiction of human gut-derived prophages, provides a substantial collection of reference sequences for forthcoming human gut phageome-related investigations, and potentially enables better risk assessment of prophage dissemination.