**4. Therapeutic potential for FVT**

In the setting of FMT, a large population of phages is transferred from the FMT donor to recipient. Feces contain approximately 109 virus-like particles per gram, a density similar to that of fecal bacteria, and phages account for upwards of 90% of all fecal virus-like particles [19]. It follows that the large transfer of fecal phages during FMT could have a physiological effect on the FMT recipient. In attempting to examine the role of fecal phages during FMT, several recent studies have not only characterized a state of virome dysbiosis in the setting of recurrent *C. difficile* infection (rCDI), but also have shown that recovery is associated with uptake of a healthy virome from the FMT donor [16, 37, 56]. A study of one FMT patient found that the patient had adopted the donor's phage community after 7 months, even when the patient's microbiome maintained a dysbiotic composition. The microbiome resembled that of the healthy donor a year later [16]. This observation that the adoption of a 'healthy' phage community precedes resolution of dysbiosis may suggest a role for phages in promoting and maintaining a healthy microbiome. This possibility is further substantiated by Zuo and colleagues who found that successful recovery from rCDI after treatment with FMT was associated with a high level of colonization by the donor's phage community in the recipient's enteric virome [37]. Another study showing long-term stability of the FMT recipient's virome found that the donor's phage community maintained colonization of the recipient 12 months after treatment [56]. Similar findings have been observed in clinical trials for FMT as an intervention for pediatric ulcerative colitis [57].

### *Fecal Virome Transplantation DOI: http://dx.doi.org/10.5772/intechopen.95469*

Additional evidence for the active role of phages during FMT comes from studies on fecal virome transplantation (FVT) showing that the sub-bacterial fraction of a FMT (i.e. bacteria removed) can manipulate the composition and structure of a recipient's microbiome [15, 18, 58]. One clinical study found that a fecal suspension that was filtered to remove bacteria, while leaving phages and other sub-bacterial particles intact, was sufficient for effective clinical treatment of rCDI and restoration of a healthy microbiome [58]. Similarly, Kao and colleagues found that a sterilized fecal filtrate was sufficient for treating rCDI [59]. Using another clinically relevant model of dysbiosis, Rasmussen and colleagues demonstrated that a FVT from lean mice was effective at reducing weight and symptoms of diabetes type 2 in obese mice fed a high-fat diet [15]. The investigators also showed that the FVT was able to increase bacterial diversity in the microbiome to the levels in lean mice. The ability for FVT to modulate microbiome composition is further supported by evidence showing that a FVT from high-fat diet-fed obese mice was sufficient for driving microbiome composition of healthy mice towards that of the high-fat diet donor [18]. The investigators also found that a FVT was sufficient for reducing small intestinal bacterial overgrowth (i.e. excess bacterial density in proximal small intestine) in obese mice to the level of healthy controls. In another recent study, investigators found that FVT also prevents necrotizing enterocolitis in preterm piglets [60]. Additionally, there is some speculation that the gut virome has a role in the "super-donor" phenomenon observed during FMT [61]. Collectively, these early studies demonstrate the therapeutic potential for FVT in multiple settings of dysbiosis.
