Viral communities of the human gut: metagenomic analysis of composition and dynamics

Varun Aggarwala, Guanxiang Liang, Frederic D. Bushman

The numerically most abundant biological entities on Earth are viruses. Vast populations prey on the cellular microbiota in all habitats, including the human gut. Here we review approaches for studying the human virome, and some recent results on movement of viral sequences between bacterial cells and eukaryotic hosts. We first overview biochemical and bioinformatic methods, emphasizing that specific choices in the methods used can have strong effects on the results obtained. We then review studies characterizing the virome of the healthy human gut, which reveal that most of the viruses detected are typically uncharacterized phage - the viral dark matter - and that viruses that infect human cells are encountered only rarely. We then review movement of phage between bacterial cells during antibiotic treatment. Here a radical proposal for extensive movement of antibiotic genes on phage has been challenged by a careful reanalysis of the metagenomic annotation methods used. We then review two recent studies of movement of whole phage communities between human individuals during fecal microbial transplantation, which emphasize the possible role of lysogeny in dispersal. Methods for studying the human gut virome are improving, yielding interesting data on movement of phage genes between cells and mammalian host organisms. However, viral populations are vast, and studies of their composition and function are just beginning.