Reproducible chemostat cultures to eliminate eukaryotic viruses from fecal transplant material

Abstract

The effect of fecal microbiota transplantation (FMT) on various gut-related diseases is intensively investigated in clinical trials. In addition to bacteria, the gut microbiome also contains eukaryotic, archaeal, and bacterial viruses (bacteriophages, in short phages), which collectively is referred to as the gut virome. Application of FMT in clinical settings is associated with a potential risk for the recipient of transferring infectious eukaryotic viruses or bacteria, despite strict screening procedures for the donor material. A safer and more targeted method to modulate the gut microbiota is therefore needed to extend the application width of FMT. Emerging evidence suggests that gut phages play a key role in maintaining a balanced gut microbiome as well as in FMT efficacy. Thus, a phageome from a cultured fecal donor microbiome may be a more efficient alternative to modulate the gut bacteriome than FMT. Here, we analyzed the dynamic changes of the viromes of mice cecal and human fecal matter inoculated chemostat cultures. Sequencing results showed that the relative abundance of eukaryotic viruses remarkably decreased during continuous cultivation, likely due to the lack of eukaryotic hosts. The corresponding phageome profiles showed dilution rate dependency, a reproducibility between biological replicates, and maintained high diversity of phages although being different from the inoculum phageome. This proof-of-concept study may constitute the first step of developing therapeutic tools to target a broad spectrum of gut-related diseases and thereby replacing FMT with a safer phage-mediated therapy.