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April 26, 2022
Viruses in the gut influence inflammatory bowel disease
At a Glance
- Viruses isolated from people with inflammatory bowel disease, or IBD, triggered inflammation in human cells and mice, while those from non-diseased guts didn’t.
- The findings suggest that transplanting certain viruses could serve as a potential treatment for IBD and other intestinal diseases.
The microorganisms normally found in the digestive system—called the gut microbiome—are thought to play an important role in intestinal diseases, such as IBD. In this painful condition, immune cells in the gut overreact to a perceived threat to the body. This leads to inflammation and tissue damage.
The roles of bacteria and fungi in the gut, and how they interact with the immune system, are better understood than the role of the intestinal virome, the collection of viruses in the gut. Studies have uncovered many changes in gut viruses in people with IBD. But whether these changes contribute to inflammation or are collateral damage caused by inflammation is not clear.
A research team led by Dr. Kate Jeffrey from Massachusetts General Hospital has been investigating this question. In their new study, they isolated and analyzed gut virome samples from people with Crohn’s disease or ulcerative colitis, the two types of IBD.
The research was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Center for Advancing Translational Sciences (NCATS). Results were published on April 8, 2022, in Science Immunology.
In human cell cultures, the viromes from people with IBD and those from people with healthy guts interacted differently with immune cells called macrophages. Viruses isolated from healthy people dampened macrophages and the inflammatory response resulting from their activity. However, those from people with IBD activated macrophages.
The team next used cultures that also contained intestinal epithelial cells, the protective cells that line the gut. Viruses isolated from people with IBD induced greater breakdown of this protective layer when compared to those taken from people with healthy guts.
Viruses from people with healthy guts were able to suppress inflammation when added to cultures containing viruses from people with IBD. Analysis of the makeup of these viruses found that people with IBD had many resident virus species not often found in people with healthy guts. These included some in the enterovirus family, which are associated with several human diseases.
To measure the relationship between the virome and inflammation in living tissues, the researchers transplanted viruses from people with IBD and from those with healthy guts into mice. Mice given the healthy viruses showed no changes in gut health. Mice given viruses from people with IBD experienced an increase in inflammation.
In a mouse model of ulcerative colitis, transplanting viruses from people with healthy guts protected against inflammation and damage. In contrast, transplanting those from people with IBD worsened tissue damage.
“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 Jeffrey.
More studies are needed to understand what viruses make up a healthy human virome. Transplanting such viruses into people with inflammatory gut diseases could serve as a potential treatment.
—by Sharon Reynolds
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References: Human enteric viruses autonomously shape inflammatory bowel disease phenotype through divergent innate immunomodulation. Adiliaghdam F, Amatullah H, Digumarthi S, Saunders TL, Rahman RU, Wong LP, Sadreyev R, Droit L, Paquette J, Goyette P, Rioux JD, Hodin R, Mihindukulasuriya KA, Handley SA, Jeffrey KL. Sci Immunol. 2022 Apr 8;7(70):eabn6660. doi: 10.1126/sciimmunol.abn6660. Epub 2022 Apr 8. PMID: 35394816.
Funding: NIH’s National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Center for Advancing Translational Sciences (NCATS); Kenneth Rainin Foundation; Harvard University; Canadian Institute of Health Research; Canada Research Chairs; Massachusetts General Hospital.