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

Gut bacteriophages profoundly impact microbial ecology and health1-3; 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.