The human gut virome: Composition, colonisation, interactions, and impacts on human health

The gut virome is an incredibly complex part of the gut ecosystem. Gut viruses play a role in many disease 9 states, but it is not yet known to what extent the gut virome impacts everyday human health. New 10 experimental and bioinformatic approaches are required to address this knowledge gap. Gut virome 11 colonisation begins at birth, becoming temporally stable over a 30-month period. The stable virome is highly 12 specific to each individual and is modulated by varying factors such as age, gender, diet, and disease state. 13 The gut virome is primarily composed of bacteriophages—predominantly crAssphage, and other 14 Caudovirales. The stability of the virome’s regular constituents is disrupted by disease. Transferring the 15 faecal microbiome and its viruses from a healthy individual can restore the functionality of the gut, and 16 alleviates the symptoms of some chronic illnesses. Investigation of the virome is a relatively novel field with 17 new genetic sequences being published at an increasing rate. Many of these present with a large percentage 18 of unknown proteins, this ‘viral dark matter’ is one of the major questions facing virologists and 19 bioinformaticians. Bioinformatics tools can be used to explore both new and existing publicly available viral 20 sequence datasets to quantify and classify viral species, but not all these tools are created equal, with some 21 being more precise, effective, and efficient than others. Here, we review the literature surrounding the gut 22 virome, how it is established, how it impacts human health, the methods used to investigate it, and the viral 23 dark matter veiling the understanding of the gut virome.