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Sequencing Study Finds Fecal Virome Diversity between Individuals

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – A study appearing online today in Nature suggests bacteria-infecting viruses in the gut do not show the same sorts of predator-prey relationships with their hosts as viruses found in some other environments.

A Washington University-led research team sequenced virus-like particles in fecal samples from a dozen women — including four sets of identical twins and their mothers. Unlike bacterial communities in feces, which tend to overlap between genetically related women, the researchers found that fecal viromes varied widely from one individual to the next, even amongst family members though each individual's own fecal virome appears to remain stable over time.

"Despite remarkable inter-personal variations in viromes and their encoded functions, intra-personal diversity is low," senior author Jeffrey Gordon, director of Washington University's Center for Genome Sciences and Systems Biology, and his co-authors wrote. "These results indicate that a predatory viral-microbial dynamic, manifest in a number of other characterized environmental ecosystems, is notably absent in the very distal intestine."

In environmental samples such as those collected from oceans or acid mine drainage systems, the researchers explained, viruses often help control bacterial populations through interactions resembling predator-prey relationships. That, in turn, can lead to selection for bacterial mechanisms to evade viruses and viral strategies that help infect bacteria.

But the relationships between viruses and bacteria living in and on the human body — and the impact of these interactions on human health — are less well understood.

"We wanted to know the nature of viruses and their lifestyle in the most populous microbial community that inhabits our bodies — the one in our gut," Gordon said in a statement.

To begin exploring these viral communities, the researchers used the Roche 454 GS FLX platform to sequence virus-like particles in fecal samples collected from 12 women: four sets of healthy identical twins and their mothers. The women, who were enrolled through the Missouri Adolescent Female Twin Study, had not taken antibiotics for at least six months prior to the study.

Additional fecal samples were collected from participants two months and one year after the study started. Over the three sampling times, the team was able to get fecal virome data for 32 of the samples.

Along with virus-like particle sequencing, the team also did 16S rRNA pyrosequencing to assess bacterial communities in the samples and used shotgun sequencing data of total fecal DNA generated for some of the samples for a previous study.

Using their virus-like particle sequence data, the researchers then developed a viral database containing more than 96 million bases representing 4,193 non-redundant genomic sequences. Of these, more than 73 percent of the sequences came from eukaryotic viruses, while almost 26 percent represented phages and prophages — viruses that infect bacteria.

And while most of the sequence reads — roughly 81 percent — came from unknown viruses, many of the identifiable viruses in the fecal samples represented bacteria-infecting phages and prophages, the team noted, particularly those infecting gut bacteria in the Firmicutes and Bacteroidetes phyla.

But while identical twins and their mothers tend to have fecal microbiomes that are more similar to one another than to non-related individuals, the same pattern did not hold for the fecal virome. Instead, the researchers detected roughly as much variation in the viral communities between twins and their mothers as they did when they compared unrelated women.

On the other hand, each individual's fecal virome appeared to be much more stable than her fecal microbiome: whereas microbial communities typically vary over time, the researchers found that more than 95 percent of the virotypes in an individual's fecal samples were the same at all three sampling times.

Together, such findings argue against a straightforward predator-prey relationship between gut bacteria and the viruses that infect them, the researchers explained, though more research is needed to home in on the interplay between bacteria and viruses in feces.

In order to get a better sense of how the fecal virome is established and maintained, the team reportedly plans to do additional studies looking at the viruses present in fecal samples from infants, including both identical and non-identical twins.

Based on their findings so far, the researchers argued that virome analyses should be also incorporated into other human microbiome studies, since such microbe-virus interactions may offer clues about how microbes contribute to human health and disease. And, they say, characterizing viral sequences in microbiomes may eventually uncover biomarkers to help track microbial communities.

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