Despite available vaccines, over 200,000 children die annually from severe diarrhea cause by rotavirus, which infects intestinal cells. A recently published study, facilitated by a research team’s lucky break, suggests bacteria in the mouse gut microbiome could actually help prevent and cure rotavirus infection.
“This is one of the first papers identifying an organism in the microbiome that can prevent and cure viral infections,” says Sarah Elizabeth Blutt, a cell biologist at Baylor College of Medicine in Houston, TX, who was not involved in the study. “It could chart a path for future research on antiviral therapy.”
To save money, immunologist Andrew Gewirtz and his colleagues at Georgia State University in Atlanta started breeding their own immunosuppressed mice rather than buying them from a commercial lab. In hopes of better understanding the mechanisms behind the clearing of chronic rotavirus infection, the researchers induced chronic infection by orally inoculating the homegrown, immune-deficient mice with rotavirus. To their surprise, the researchers observed that the inoculated mice were completely resistant to rotavirus infection. But as expected, commercial lab-bred mice developed the chronic infection.
Gewirtz’s team then housed homegrown rotavirus-resistant mice with commercial lab-bought mice that they had orally infected with rotavirus. The latter were cured of the induced chronic rotavirus infection. They saw the same result when they conducted fecal transplants, inoculating immune-suppressed lab mice with feces from resistant mice. “We realized there was something being transferred,” says Gewirtz.
The team then measured virus antigens in the feces of infected homegrown and infected commercial mice on a daily basis. One day after infection, rotavirus antigen in feces of the lab-bought mice shot up, indicating the mice were infected. But after 10 days, the homegrown mice still showed no signs of infection.
In another test, the team compared two groups of six lab-bought mice chronically infected with rotavirus. One group was given a fecal transplant from resistant homegrown mice; after six days the mice were cured. The team gave the other set of mice a fecal transplant from lab-bought mice; the mice remained infected throughout the experiment. “It’s a pretty dramatic difference,” says Gewirtz.
Using high-throughput techniques, the team sequenced and compared the microbiomes of the resistant and susceptible mice. They discovered that segmented filamentous bacteria (SFB) were present in the former but not the latter, suggesting that SFB drove the resistance to rotavirus.
Gewirtz thinks these bacteria are a normal part of the mouse microbiota. “We tested mice from pet stores, and they all have SFB. Most rodents in the wild have SFB,” he explains, noting that the commercial lab mice probably didn’t host the bacteria due to the extremely sterile environment in which they were bred.
Gut microbiota are known to prevent infection by pathogenic bacteria, but their role in protecting against viral infection is less clear.
It wouldn’t make sense to administer SFB directly to humans as a prevention or cure—the bacterium can cause an immune response related to chronic inflammatory diseases, such as inflammatory bowel disease and arthritis. Instead, Gewirtz’s team is trying to figure out the mechanisms by which SFB protects against rotavirus—hoping to perhaps co-opt them as part of a future treatment. The researchers did observe that the bacteria stopped the virus from binding well to epithelial intestinal cells in in vitro, pointing to an avenue for further investigation.
Gewirtz and his team are also aiming to find other bacteria that could activate the same mechanisms as SFB without the harmful side effects. They plan to examine humans who are naturally resistant to rotavirus. Past work suggests that susceptibility to rotavirus infections varies among geographical locations and within populations. While some of that variation stems from general health, the roots of much of it remain unknown, says Gewirtz. “We think that differences in bacterial composition might be playing a role in differential susceptibility,” Gewirtz says. Perhaps there would be a way to harvest the “safe” bacteria from the guts of rotavirus-resistant people.
“The intestinal microbiota is an incredibly diverse chemical factory producing all sorts of things,” says Gewirtz, noting that these microbes have interacted for millions of years. “So we think that this is a logical place to search for antiviral compounds.”