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Viruses have an understandably bad reputation. But deep in our digestive system, a lot of them are quietly working to keep us healthy. This “gut virome” is a key part of the overall microbiome—the vast collection of microbes that play a crucial role in our digestion, immunity, and overall health.

“The bacteria component of the microbiome is well known,” says Tao Zuo, a microbiologist at Sun Yat-sen University in China. “But the virome we don’t really know much about.”

This is partly because the virome makes up only about 0.1 percent of the microbiome’s total biomass, Zuo explains. And viruses mutate quickly, making their genetic material harder to isolate for study. To get a better understanding, Zuo and his colleagues pulled together a wealth of research data to catalog how the gut virome changes with age, diet, and environment.

Their review, published in Precision Clinical Medicine, particularly focuses on bacteriophages—viruses that infect bacteria and make up more than 95 percent of the virome. These viruses sometimes benefit us by infecting and killing harmful gut bacteria. But they can also strengthen pathogens—“for example, if a bacteriophage carries a gene that offers resistance to antibiotics,” says virologist Jelle Matthijnssens, who specializes in virome research at Belgium’s Catholic University of Leuven (KU Leuven) and was not involved in the review.

The study’s authors show how an individual’s virome is constantly developing based on genetics and environment. At birth, infants’ bacteriophages often vastly outnumber their microbiome’s bacteria, but this begins to change with exposure to the outside world and as the gut develops. During adolescence, bacterial populations develop further from hormone shifts and accrued exposure to other microbes. By adulthood, healthy individuals host a delicate and mutually beneficial equilibrium of bacteriophages and bacteria.

Certain bacteriophages that help maintain this balance are extremely reactive to environmental factors such as diet and air quality, and they also respond to their host’s inflammation levels, immune signaling, stress hormones, and more. Factors such as exposure to certain drugs and poor diet can trigger an imbalance that reduces virome diversity. This, in turn, has been associated with disorders such as inflammatory bowel disease. In elderly people, an aging immune system and increased metabolic stress can further throw this system out of whack and increase viral numbers, potentially contributing to age-related diseases.

Understanding these aging and environmental effects may someday contribute to clinical applications such as “phage therapy,” the researchers say—but much more research is needed.

“A key challenge is distinguishing causality from correlation,” says Evelien Adriaenssens, a microbiologist at the Quadram Institute in England, who was not involved in the new study. “Each individual’s virome is unique…, so we cannot make sweeping statements about the health of an individual by looking at their virome alone.”

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Thomas Fuchs

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