What is already known on this topic
The communities of viruses inhabiting the human gut — collectively known as the human virome — are established at birth, and feces can contain about ten billion virus-like particles per gram. However, it’s unclear whether and how the human virome contributes to health and disease.
What this research adds
Researchers analyzed the gut viromes of either healthy people or individuals with inflammatory bowel disease (IBD), a group of conditions characterized by chronic inflammation of the gastrointestinal tract. The researchers found that the gut virome from people with IBD was perturbed, with an increase in enterovirus B species. When transferred in mice, gut viromes from people with IBD aggravated colitis, whereas viromes from non-IBD individuals protected the gut against inflammation.
Conclusions
The findings suggest that alterations of the gut virome contribute to the development of IBD. Thus, the virome might be used as a disease biomarker or in therapeutic approaches.
Scientists have known that billions of viruses reside in the human gut, but the role of these viral communities — collectively known as the human virome — remains a mystery. A new study suggests that alterations of the gut virome contribute to the development of a group of conditions characterized by long-term inflammation of the gastrointestinal tract.
The findings, published in Science Immunology, indicate that the human virome may be used as a disease biomarker for some intestinal conditions or in therapeutic approaches.
“Our work provides a missing functional link that our collective virome is an important contributor to human health, but when perturbed does provoke inflammation in IBD and conceivably many other diseases,” says study senior author Kate Jeffrey at Harvard Medical School.
The human virome is established at birth, and feces can contain about ten billion virus-like particles per gram. Alterations of the virome have been reported in several conditions, including colorectal cancer, cystic fibrosis, and inflammatory bowel disease (IBD) — an umbrella term for conditions characterized by chronic inflammation of the gastrointestinal tract. However, it’s unclear whether and how the human virome contributes to health and disease.
To address this question, Jeffrey and her colleagues analyzed the viromes recovered from the guts of either healthy people or individuals with IBD.
Inflammation trigger
First, the researchers isolated viruses from surgical tissue of the human colon; then, they delivered the viruses to immune cells. Viruses from the gut of healthy people had anti-inflammatory effects, whereas those isolated from the inflamed intestines of people with IBD triggered inflammation.
When mixed with the virome of people with IBD, viruses collected from healthy colon tissues were able to suppress inflammation, the researchers found. “These data demonstrate the potential utility of viruses in a healthy intestine, or the anti-inflammatory immune response to it, to suppress the inflammatory capacity of viruses in a diseased intestine,” the researchers say.
Further experiments showed that mice whose viromes were replaced with those from healthy people were protected against gut inflammation. In contrast, viromes from people with IBD triggered inflammation and exacerbated colitis in the mice’s guts. Guts colonized with these viromes had a reduced integrity of the intestinal barrier, the researchers found.
Disease-driving viruses
The team also identified viruses unique to people with IBD: samples from the inflamed intestines of IBD patients had high levels of a group of viruses called enteroviruses, which were missed in previous gut virome studies. “Enterovirus B infection has already been shown to associate with type 1 diabetes, indicating that prolonged infections with these viruses, with a fecal-oral route, might contribute to development of chronic inflammatory disorders more broadly,” the researchers say.
Previous studies have shown that enterovirus B can be sensed by a receptor called MDA5, and mutations in the gene encoding this receptor are linked with IBD. Jeffrey and her team found that human intestinal epithelial cells that harbor mutations in MDA5 showed greater damage when exposed to viromes from people with IBD.
Eliminating or replacing disease-driving intestinal viruses with health-promoting viruses may be beneficial for people with IBD, the researchers say.
