The human gut virome: a multifaceted majority

Abstract

Here, we outline our current understanding of the human gut virome, in particular the phage component of this ecosystem, highlighting progress, and challenges in viral discovery in this arena. We reveal how developments in high-throughput sequencing technologies and associated data analysis methodologies are helping to illuminate this abundant 'biological dark matter.' Current evidence suggests that the human gut virome is a highly individual but temporally stable collective, dominated by phages exhibiting a temperate lifestyle. This viral community also appears to encode a surprisingly rich functional repertoire that confers a range of attributes to their bacterial hosts, ranging from bacterial virulence and pathogenesis to maintaining host-microbiome stability and community resilience. Despite the significant advances in our understanding of the gut virome in recent years, it is clear that we remain in a period of discovery and revelation, as new methods and technologies begin to provide deeper understanding of the inherent ecological characteristics of this viral ecosystem. As our understanding increases, the nature of the multi-partite interactions occurring between host and microbiome will become clearer, helping us to more rationally define the concepts and principles that will underpin approaches to using human gut virome components for medical or biotechnological applications.

Keywords: bacteriophage; dysbiosis; human gut microbiome; metagenomics; phage-encoded functions; virus-like particles.

FIGURE 1

Overview of available human gut phage genomic sequences. (A) Major phylogenetic divisions of bacteria within the human gut microbiome. This community is dominated by members of the Bacteroidetes and Firmicutes. (B) Distribution of 611 phage genomes available on NCBI by phylogenetic division of host bacteria, and association with the human gut. Phages have been classified as gut associated (red bars), non-gut (blue bars) or remain unclassified (gray bars); based on Blastn searches of 168 metagenomic data sets of human or environmental origin. Adapted from Ogilvie and Hirsch (2012).

FIGURE 2

Model of phage mediated-dysbiosis. Genetic and environmental factors combine to present a gastrointestinal mucosal environment which modifies the adherent phage community. The anti-microbial properties of these mucosal phages – bacteriophage adherence to mucus (BAM) model proposed by Barr et al. (2013a) – are altered compared to healthy individuals leading to microbial dysbiosis, e.g., via proliferation of pro-inflammatory bacterial types and/or depletion of selected protective bacterial types. Invasion of the epithelial cell layer by bacteria may create a cellular environment in which the complex microbial-epithelial interactions are disrupted resulting in, e.g., alterations in gene expression and signaling pathway activation as well as disequilibrium of innate and adaptive immune responses. Top panel of figure inspired by Barr et al. (2013a).