Long-read sequencing reveals extensive gut phageome structural variations driven by genetic exchange with bacterial hosts

Genetic variations are instrumental for unraveling phage evolution and deciphering their functional implications. Here we explore the underlying fine-scale genetic variations in the gut phageome, especially structural variations (SVs). By employing virome-enriched long-read metagenomics sequencing across 91 individuals, we identified a total of 14,438 non-redundant phage SVs, and revealed their prevalence within the human gut phageome. These SVs are mainly enriched in genes involved in recombination, DNA methylation, and antibiotic resistance. Strikingly, a substantial fraction of phage SV sequences share close homology with bacterial fragments, with most SVs enriched for horizontal gene transfer (HGT) mechanism. Further investigations showed that these SV sequences were genetic exchanged between specific phage-bacteria pairs, particularly between phages and their respective bacterial hosts. Temperate phages exhibits a higher frequency of genetic exchange with bacterial chromosomes then virulent phages. Collectively, our findings provide novel insights into the genetic landscape of the human gut phageome.