Gut bacteriophages: fellow travellers or drivers of the microbiome?

The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable attention, comparatively little is known about the composition and physiological significance of equally prominent viral populations (the virome). Up to 10^12 viruses reside in the human gut. More than 90% of them are bacteriophages (the phageome). Metagenomic analysis of the phageome remains challenging since the vast majority of bacteriophages are novel, previously uncultured and target unknown bacterial hosts.Contrary to the expectations the phageome predominantly consists of virulent rather than temperate bacteriophages, which are predicted to target major taxonomic groups of anaerobic gut bacteria. Despite their virulent nature, these phages are highly persistent in the gut and form stable communities (persistent personal viromes - PPVs) with striking levels of individuality between human subjects. A specific group of mostly uncultured bacteriophages termed crAssphages is especially predominant, with levels reaching 10^11 pfu or 20% of total DNA content in the gut. An unusual type of interaction with the bacterial host underpins the unique ability of crAssphage to maintain long term persistence in the human gut.Specific alterations of bacteriophage communities can be associated with inflammatory bowel disease (IBD) and recurrent C. difficile infection (CDI), while faecal microbial transplantation (FMT) in CDI leads to clinical remission, paralleled by restoration of healthy phage communities and stable engraftment of specific donor phages.The significance of bacteriophages in the gut microbiome remains to be established. One can hypothesize however, that selective pressure exerted by phage infection on one hand, and phage-mediated horizontal gene transfer on the other hand, strongly contribute towards maintaining taxonomic and functional diversity of the microbiome, its resilience to stress and adaptability to changes in the gut environment.