A previously undescribed highly prevalent phage identified in a Danish enteric virome catalogue

Abstract Background: Gut viruses are important players in the complex human gut microbial ecosystem. Recently, the number of human gut virome studies is steadily increasing, however we are still only scratching the surface of the immense viral diversity as many wet lab and bio-informatics challenges remain. In this study, 254 virus-enriched faecal metagenomes from 204 Danish subjects were used to generate a Danish Enteric Virome Catalogue (DEVoC) of 12,986 non-redundant viral genome sequences encoding 190,029 viral genes, which formed 67,921 orthologous groups. The DEVoC was used to characterize the composition of the healthy DEVoC gut viromes from 46 children and adolescents (6-18 years old) and 45 adults (40 -73 years old).Results: The majority of DEVoC viral sequences (67.3 %) and proteins (61.6 %) were not present in other (human gut) viral genome databases. Gut viromes of healthy Danish subjects mostly consisted of phages. While 39 phage genomes (PGs) were present in more than 10 healthy subjects, the degree of viral individuality was high. Among the 39 prevalent PGs, one was significantly more prevalent in the paediatric cohort, whereas two were more prevalent in adults. In 1,880 gut virome samples of 27 studies from across the world, the 39 prevalent PGs reveal several age-, geography- and disease-related prevalence patterns. Two PGs also showed a remarkably high prevalence worldwide – a crAss-like phage (20.6% prevalence), belonging to the tentative AlphacrAssvirinae subfamily, genus I; and a previously undescribed circular temperate phage (14.4% prevalence), named LoVEphage (because it encodes Lots of Viral Elements). A de novo assembly of selected public datasets generated an additional 18 circular LoVEphage-like genomes (67.9-72.4 kb). CRISPR spacer analysis suggested Bacteroides as a host genus for the LoVEphage, and a closely related prophage was identified in Bacteroides dorei, further confirming the host.Conclusions: The DEVoC, the largest human gut virome catalogue generated from consistently processed faecal samples, facilitated analysis of healthy Danish human gut viromes and we foresee that it will benefit future analysis on the roles of gut viruses in human health and disease. The identification of a previously undescribed prevalent phage illustrates the usefulness of developing a virome catalogue.