Review article: the human intestinal virome in health and disease

Abstract

Background: The human virome consists of animal-cell viruses causing transient infections, bacteriophage (phage) predators of bacteria and archaea, endogenous retroviruses and viruses causing persistent and latent infections. High-throughput, inexpensive, sensitive sequencing methods and metagenomics now make it possible to study the contribution dsDNA, ssDNA and RNA virus-like particles make to the human virome, and in particular the intestinal virome.

Aim: To review and evaluate the pioneering studies that have attempted to characterise the human virome and generated an increased interest in understanding how the intestinal virome might contribute to maintaining health, and the pathogenesis of chronic diseases.

Methods: Relevant virome-related articles were selected for review following extensive language- and date-unrestricted, electronic searches of the literature.

Results: The human intestinal virome is personalised and stable, and dominated by phages. It develops soon after birth in parallel with prokaryotic communities of the microbiota, becoming established during the first few years of life. By infecting specific populations of bacteria, phages can alter microbiota structure by killing host cells or altering their phenotype, enabling phages to contribute to maintaining intestinal homeostasis or microbial imbalance (dysbiosis), and the development of chronic infectious and autoimmune diseases including HIV infection and Crohn's disease, respectively.

Conclusions: Our understanding of the intestinal virome is fragmented and requires standardised methods for virus isolation and sequencing to provide a more complete picture of the virome, which is key to explaining the basis of virome-disease associations, and how enteric viruses can contribute to disease aetiologies and be rationalised as targets for interventions.

Figure 1

The mammalian intestinal virome comprises viruses that infect eukaryotic and prokaryotic cells. It is established soon after birth and is dominated by viruses that infect bacteria (ie, phages). The virome establishes a mutualistic relationship with eukaryotes/prokaryotes, contributing to intestinal homeostasis by influencing microbial ecology and host immunity. Composition of the virome is influenced by numerous factors that affect viruses directly (infection) or change host‐cell populations (eg, antibiotics, diet). Members of the virome may contribute to the pathogenesis of certain diseases via microbial host lysis leading to dysbiosis, infection of epithelial cells, and/or translocation of the compromised or damaged mucosal barrier to gain access to underlying tissues and immune cells, leading to immune activation. Dysbiosis can be defined as a microbial imbalance or any changes to the composition of resident microbial communities relative to the community found in healthy individuals.101, 102, 103 Virome association with certain disease states is characterised by changes in diversity, and predominance of specific virotypes (eg, members of the order Caudovirales in IBD)

Figure 2

Breakdown of complete genomes of members of the order Caudovirales (dsDNA viruses, no RNA stage) available from NCBI Genome on November 21, 2016 (n = 1943). The number of publicly available Caudovirales genomes had only increased to 2044 by July 6, 2017. Genera of prokaryotes (with some families and higher taxa) infected by phages are shown around the chart; colours correspond to phyla (kingdom in the case of the Archaea) of prokaryotes infected by different phages. Aggregated data are shown for each of the three families of the order Caudovirales in the large plot. Myoviridae, n = 538 complete genomes; Siphoviridae, n = 1063 complete genomes; Podoviridae, n = 342 complete genomes. Larger versions of the pie charts shown in this figure are available in Supporting Information