Engrafting gut bacteriophages have potential to modulate microbial metabolism in fecal microbiota transplantation

Fecal microbiota transplantation (FMT) is widely used to treat severe infections and investigated for the treatment of complex diseases. The therapeutic efficacy of FMT is related to the successful engraftment of bacteriophages from healthy donors to recipients. However, gut bacteriophage contributions to FMT engraftment and treatment outcomes remain unclear. The gut phageome from previously published metagenomes of donors and recipients across 23 FMT studies was assembled and functionally annotated for a meta-analysis. Gut phageome profiles of FMT recipients, especially those with recurrent Clostridioides difficile infection (rCDI), shifted toward donor phageomes, accompanied by increased phageome alpha diversity. Engraftment of donor phages varied between recipient conditions with the highest engraftment rate, overrepresented by putative temperate phage, in patients with rCDI. Consistently, a higher proportion of auxiliary metabolic genes (AMGs), with the potential to support and modulate bacterial metabolism, were annotated on putative temperate phages. FMT leads to significant taxonomic, functional, and lifestyle shifts in recipient phageome composition. Future FMT studies should include gut phageome characterization and consider it as a potential factor in microbial community shifts and treatment outcomes. Video Abstract.