In humans, norovirus is known to many a traveler as the cruise ship virus which causes gastrointestinal disease. In mice, however, it is a harmless denizen of the gut that does not usually cause overt disease in the animals.

In fact, researchers from New York University have now shown, murine norovirus could protect animals from gut damage.

The findings establish viruses as a component of the beneficial microbiome.

"The microbiome can include multiple kingdoms of life," New York University's Ken Cadwell told reporters during a conference call to discuss the findings, which appeared in the Nov. 19, 2014, advance online edition of Nature. "The bacterial component is the one that everyone has heard of."

But increasingly, "people are picking up on the fact that there are not just bacteria there."

Fungi, too, are part of the microbiome, and "mycobiome" research has implicated them in inflammatory bowel disease and Crohn's disease (See BioWorld Today, June 10, 2012.)

And even parasites can be beneficial to the human immune system.

"I'd hate to call [parasites] a part of the microbiome just yet . . . that would be a little more controversial," Cadwell said. But there is research implicating the branch of the immune system that normally deals with such parasites in autoimmune disease. (See BioWorld Today, April 19, 2006.)

So far, less is known about the role that viruses play in the microbiome. Partly, that is because viruses have been more challenging to sequence. "Detecting a virus in the gut is like finding a needle in a haystack," Cadwell said – the relative sizes of bacterial and viral genomes means that sequencing whole samples gives researchers mostly bacterial genomes.

Not that it's always so easy to tell. "When you just look at a sequence it's very difficult to know whether it came from a virus," Cadwell said, and it is all but certain that the human-colonizing virome includes as-yet unidentified species.

Detecting viruses has become easier with the development of new bioinformatics methods, which have been steadily improving over the past few years.

Cadwell and his coauthors Elisabeth Kernbauer and Yi Ding, though, came by their data via a different route. "Our technical advance was that we put this virus into a germ-free mouse in an isolator," Cadwell said.

Germ-free mice, which are born without a microbiome and live in sterile conditions so they cannot acquire one, are used to study the broad effects of the microbiome on both disease and normal development. Such animals have developmental defects both in their intestines and in their immune system.

In their experiments, the team allowed just a single microorganism to colonize the otherwise still germ-free mice: murine norovirus.

They found that the virus was able to partially compensate for the absence of bacteria. Mice that were inoculated with norovirus, either from birth on or at the age of 10 days, had fewer gut and immune system abnormalities than their fully germ-free cousins.

The beneficial effects of norovirus were also evident under less extreme conditions than total sterility. Norovirus was also beneficial in adult animals whose microbiomes were wiped out by antibiotic treatment.

Finally, norovirus infection protected mice that lacked bacteria from toxic effects of treatment with the chemical DSS. DSS damages the colon, and in mice that do not have a microbiome, the chemical can be fatal. But mice whose colon contained norovirus but no bacteria survived treatment with DSS.

Cadwell and his colleagues plan to look at the molecular details of how norovirus benefits the gut. Initial analyses have shown that the presence of norovirus changes gene expression patterns related to blood vessel formation, immunity and metabolic state. Knockout mice missing an interferon receptor were not protected by norovirus administration, showing that interferon, which is typically produced in response to viral infection, is important for the effects.