Long-read metagenomics reveals phage dynamics in the human gut microbiome

Gut bacteriophages profoundly impact microbial ecology and health^1-3; yet, they are understudied. Using deep long-read bulk metagenomic sequencing, we tracked prophage integration dynamics in stool samples from six healthy individuals, spanning a 2-year timescale. Although most prophages remained stably integrated into their hosts, approximately 5% of phages were dynamically gained or lost from persistent bacterial hosts. Within a sample, we found that bacterial hosts with and without a given prophage coexisted simultaneously. Furthermore, phage induction, when detected, occurred predominantly at low levels (1-3× coverage compared to the host region), in line with theoretical expectations⁴. We identified multiple instances of integration of the same phage into bacteria of different taxonomic families, challenging the dogma that phages are specific to a host of a given species or strain⁵. Finally, we describe a new class of 'IScream phages', which co-opt bacterial IS30 transposases to mediate their mobilization, representing a previously unrecognized form of phage domestication of selfish bacterial elements. Taken together, these findings illuminate fundamental aspects of phage-bacterial dynamics in the human gut microbiome and expand our understanding of the evolutionary mechanisms that drive horizontal gene transfer and microbial genome plasticity.