The human gut virome is highly diverse and composed mostly of phages. Yet, despite the vast diversity of gut viral species (>200,000+) identified so far, of which >90% are phage, there are a relatively low number of bacterial species (~4,500) that have been found in the human gut. This high ratio of phage species to bacterial species suggests that many of these phage species must share the same host. Here, we introduce the concept of using viral predation guilds, i.e. groups of viruses that exploit the same hosts, instead of taxonomy-based analyses to study the human gut virome. We hypothesized that given the high inter-individuality of the virome and the low number of bacterial species in the human gut, individuals most likely share a high proportion of viral guilds despite distinctly different viral species. In order to test our hypothesis, we analyzed 7,597 gut metagenomes from the Finnish FINRISK 2002 Cohort. Across the samples, we identified 70,864 viral contigs that de-replicated into 134,507 viral species and then with existing gut viral databases to get a total of 339,167 viral species. In total, 74.7% of the viral species could be assigned to 1,355 guilds based on host genus-level taxonomy. Like previously reported, we observed high inter-individuality with only 309 viral species found in at least 1,000 cohort individuals and only 2 found in over 6,000. Thus, it was not surprising that analyses at the viral species-level revealed no distinct clustering of viral communities. In contrast, viral guild-level clustering of individuals revealed three distinct viral community types, one that was dominated by phages in the Bacteroides guild, one that was dominated by phages in the Prevotella guild, and the last where most phages belonged to the Bacteroides guild, but also has high numbers of phages in other guilds. These viral community types strongly correspond to well-known gut bacterial community types sometimes called enterotypes, that separate Prevotella-driven samples from the rest, suggesting that guild-level analyses may be better suited for studying viral ecological interactions within the human gut. Overall, these results indicate that studying viral communities at the guild level may provide a higher functional resolution in some ecosystems such as the human gut.
