## 3 Intestinal Bacteriophages and Faecal Virome Transplants
### The Phageome of the Gut and the Surprising Prevalence of crAssviridae
This prototypical crAssphage has been subsequently reclassified as _Carijovirus communis_[81], and it is now known that the crAssphage family is a highly diverse taxonomic unit, mostly including difficult-to-culture phages that tend to be found in the human gut in large quantities, being routinely identified in about 50% of individuals in certain populations and sometimes making up nearly 90% of the total viral DNA load in faeces [80; 82]. Members of this unit have also been identified in many other habitats, from the guts of termites [83] to the waters of the Arctic Ocean [84]. CrAssophages are also characterised by somewhat unique host-predator dynamics that are--similarly to the previously mentioned phage interactions--consistently inconsistent with the Lotka-Voltera model. Perhaps surprisingly, crAssphages, while usually not inducing the formation of plaques in plaque assays, like most lytic viruses, were generally thought to be incapable of classic lysogeny, lacking suitable lysogeny-associated genes [85], and therefore their ample presence and persistence within the gut had to be explained by other mechanisms. An interesting host-phage relationship can be observed in \(\Phi\)CrAss001, now known as _Ketishuovirus primarius_[81], which was the first crAssphage family member to be successfully isolated and cultured [85]. The virus infects _Bacteroides intestinalis_, but a certain share of _B. intestinalis_ subpopulations can spontaneously convert to a subtype expressing a different capsular polysaccharide, which prevents infection by _Ketishuovirus_ crAssphage--thus, at all times, a portion of the bacterial population is susceptible to the virus and the lysis of its members yields new virions, while another portion remains resistant to infection and can proliferate undisturbed [86]. The mechanism of switching between capsular polysaccharides, dubbed phase variation, has been observed before and is apparently regulated by genetic or epigenetic factors [87]. This explains the difficulty in identifying the phage in vitro. Even though the original study describing _Kehisluvirus primarius_ did report the observation of clear plaques on agar media in some circumstances, in others--such as after prolonged coculture of host and phage--the opacity caused by the continuous growth of resistant wild-type _B. intestinalis_ lineages within the plaques makes them barely noticeable. Some crAssviruses have not been observed to form visible plaques at all, as is the case with \(\Phi\)CrAss002, now known as _Jalgtovirus secundus_, which infects _Bacteroides xylanilovens_[81; 88]. This virus exhibits a different, perhaps even paradoxical, dynamic with its host--in vitro cultures, the titre of the introduced virus does not increase (and, in fact, tends to decrease) for up to 2 or 3 days after the introduction of viral lysate into the culture until its count finally rebounds, achieving relatively high values of \(10^{8}\)-\(10^{9}\) copies per millilitre; the titre then remains essentially the same for weeks [88]. Moreover, neither this initial lag in viral proliferation nor the subsequent drastic increase in viral count seem to affect the numerosity of host bacteria. Therefore, faced with these confusing reports about a group of phages that should supposedly be strictly lytic given their apparent lack of lysogeny-enabling genes, other models have to be considered. A recent publication postulated that the prototypical _Carjivirus communis_ crAssphage, while not integrating with the host chromosome in accordance with classic lysogeny models, is able to persist within the bacterial cell as a prophage-like plasmid molecule [89]. This is consistent with many previous reports of phages that exist as plasmids instead of integrating with the host chromosome [90; 91]. This discovery of the phage-plasmid lifestyle of _Carjivirus communis_--the first and to date only crAssphage proved to possess this characteristic--has tremendous implications for our understanding of phage-host coexistence in vivo.