The human gut virome: Inter-individual variation and dynamic response to diet

Abstract

Immense populations of viruses are present in the human gut and other body sites. Understanding the role of these populations (the human “virome”) in health and disease requires a much deeper understanding of their composition and dynamics in the face of environmental perturbation. Here, we investigate viromes from human subjects on a controlled feeding regimen. Longitudinal fecal samples were analyzed by metagenomic sequencing of DNA from virus-like particles (VLP) and total microbial communities. Assembly of 336 Mb of VLP sequence yielded 7175 contigs, many identifiable as complete or partial bacteriophage genomes. Contigs were rich in viral functions required in lytic and lysogenic growth, as well as unexpected functions such as viral CRISPR arrays and genes for antibiotic resistance. The largest source of variance among virome samples was interpersonal variation. Parallel deep-sequencing analysis of bacterial populations showed covaration of the virome with the larger microbiome. The dietary intervention was associated with a change in the virome community to a new state, in which individuals on the same diet converged. Thus these data provide an overview of the composition of the human gut virome and associate virome structure with diet.

Human oral viruses are personal, persistent and gender-consistent

“…nih.gov/refseq/; Supplementary Figure 3). Similar to results found for viromes from different environments (Desnues et al, 2008;Minot et al, 2011;Roux et al, 2012;Wommack et al, 2012;Minot et al, 2013;Yoshida et al, 2013), the majority of the contigs had no known viral homologues. Approximately 32.7±5.9% (range from 20.3 to 48.0%) of the virome contigs were homologous to known viruses, depending on the subject and time point analyzed (Supplementary Figure 3).…”

“…Our findings of a large number of viral genotypes that persist over time are contrary to that presented in our prior study (Pride et al, 2012a); however, they highlight several difficulties encountered when examining large and complex metagenome data sets. These difficulties include the following: (1) assembly related overestimation of viral genotypes, as we likely observed in our previous study (Pride et al, 2012a), (2) lack of available homologs to aid in the identification of virome constituents (Desnues et al, 2008;Minot et al, 2011;Roux et al, 2012;Wommack et al, 2012;Minot et al, 2013;Yoshida et al, 2013) and (3) the relative lack of statistical tools to discern differences in virome compositions. We did not perform detailed comparisons of viral genotypes and the bacteria present in each subject because our BLAST-based techniques for characterizing viruses generally are considered insufficient to accurately predict the hosts of each virus.…”

“…In a study of four adult pairs of twins and their mothers, gut viral communites were not associated with the genetic relationship between individuals (Reyes et al, 2010). In a more recent study of gut viromes, six individuals were sampled at four time points over a relatively short 8-day period and demonstrated substantial individuality in their virome compositions (Minot et al, 2011). In another study, a healthy individual's colonic microbiome was sampled 16 times over 2.4 years, demonstrating that much of the viral taxonomy of the gut was persistent (Minot et al, 2013).…”

“…Many of the viruses in these communities are bacteriophage (Breitbart et al, 2003;Minot et al, 2011;Willner et al, 2011;Pride et al, 2012a;Minot et al, 2013), likely secondary to the abundance of bacterial cells compared with eukaryote cells in these communities. Viruses likely have a key role in microbial population structures by altering the composition of bacterial communities (Duerkop et al, 2012).…”

“…Viromes from rodent feces harbor insect and plant viruses (Phan et al, 2011), suggesting that diet has substantial effects on viral encounters. Whereas viral communities are less well studied in humans, there also is evidence that the gut virome may respond to dietary changes (Minot et al, 2011). Host genetic factors as well as environmental variables such as sex and hormonal fluctuations have also been linked to the human microbiome, as has been demonstrated by genderspecific differences in the bacterial biota of the gut (Mueller et al, 2006;Li et al, 2008) and the oral cavity (Slots et al, 1990;Umeda et al, 1998).…”