A Viral Wonderland in the Human Gut

14 July 2010 1:39 pm

Snowflakes haven't cornered the market on uniqueness. Researchers report that human guts harbor viruses as unique as the people they inhabit; the viral lineup differs even between identical twins. The discovery offers a first glimpse at the previously unknown viruses and their surprisingly friendly relationships with their hosts.

Microbiologists have known since the late 19th century that human intestines are a crowded and complicated place. Our bacterial denizens outnumber our cells, and many help break down foods and fight off pathogens. For the past decade, microbiologist Jeffrey Gordon of Washington University in St Louis has been mapping the gut's microbial landscape. His studies have linked intestinal bacteria to obesity and have shown that families tend to share their microbial makeup. But scientists hadn't yet explored whether phages—viruses that infect bacteria—were part of this shared community.

Led by graduate student Alejandro Reyes, Gordon's team analyzed fecal samples from four sets of Missouri-born female identical twins and their mothers. The researchers collected and purified the poop three times over the course of a year—to better track the microbial community's changes over time—and then sequenced the viral DNA, or viromes, the poop contained. Only 20% of the viromes matched existing databases; the rest came from previously unknown viruses. And each woman's set of viromes was distinctive, differing even from the viromes of her identical twin, the researchers report in the 15 July issue of Nature. Unlike their bacterial profiles, which overlapped by about 50% (significantly more than between strangers), identical twins had no more viruses in common than did unrelated people.

Equally surprising, Gordon says, was the communities' consistency: the viral makeup changed less than 5% over the course of the year, and the viromes of the most abundant phages changed less than 1%. Rapidly changing viromes would have signaled an "arms race" in which threatened bacteria were adapting to survive phage attacks, and the phages were adapting to avoid bacterial defenses. "The fact that the viromes didn't change," says Gordon, "suggests this is a temperate environment" in which the bacteria and their phages coexist in peace.

That may be because the viruses are actually helping the bacteria. When the viruses latch onto gut bacteria, they take some of their host's genetic material and can change it or move it to other hosts, bringing new and potentially advantageous functions to the bugs. The researchers found that many of the genes the phages carry and transfer are beneficial to the bacteria; some may help them repair cell walls, for example. In return, the bacteria, which don't die from the infections, provide an improved cellular factory to make new viruses.

The researchers don't know where the viruses come from or what causes viromes to differ so dramatically from person to person. But their data indicate that there is a huge diversity of these viruses, and that could explain why even closely related people can harbor very different populations.

Gordon says that understanding the details of the phage-bacteria relationship could help gauge the health of a patient's gut community, because the phages are sensitive to changes in their hosts. But "we still have a lot to learn about viruses" before we can expect any practical applications, says microbiologist Edward DeLong of the Massachusetts Institute of Technology in Cambridge. "This is just a first peek," he says, "but it's a remarkable one. It's the first high-resolution picture of the bacterial-viral dynamic in the human ecosystem, in a huge part of our own ecology that remains terra incognita."

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