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

Background Fecal microbiota transplantation (FMT) is widely used to treat severe infections and investigated for treatment of complex diseases. The therapeutic efficacy of FMT is related to successful engraftment of bacteriophages from healthy donors to recipients. However, gut bacteriophage contributions to FMT engraftment and treatment outcomes remain unclear. Methods The gut phageome from previously published metagenomes of donors and recipients across 23 FMT studies was assembled and functionally annotated for a meta-analysis. Results Gut phageome profiles of FMT recipients, especially those with rCDI, shifted towards donor phageomes, accompanied by increasing phageome alpha diversity. Engraftment of donor phages varied between recipient conditions with highest engraftment rate, overrepresented by temperate phage, in patients with rCDI. Consistently, a higher proportion of auxiliary metabolic genes (AMGs), with potential to support and modulate bacterial metabolism, were annotated on temperate phages. Conclusions 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.