Are all viruses harmful? Research finds that they can help build intestinal immunity

An imbalance in fecal virome has been reported in patients with ulcerative colitis (UC), Crohn's disease (CD), and other types of inflammatory bowel disease (IBD).

However, it is unclear whether fluctuations in viral populations have a mechanistic role in these diseases.

Kate L. Jeffrey, PhD, a scientist in the Massachusetts General Hospital Center for Inflammatory Bowel Disease Research, Fatemeh Adiliaghdam, PhD, a researcher in Dr. Jeffrey's laboratory, and colleagues provide the first important evidence that a healthy gut viral population can help build gut immunity in humans -- in stark contrast to the belief that all viruses are bad.

Equally exciting, the viromes from IBD patients triggered inflammation both in the lab and in mice. The team discusses the implications of these findings for virus-based treatments for IBD in the journal Science Immunology.

(Source: Pixabay)

Since the virus requires host cells to replicate, the researchers chose to study colon tissue. They isolated the virus from healthy volunteers and resected tissue samples from patients with UC or CD and delivered it to human macrophages or intestinal epithelial cells.

In both types of experiments, viruses from the healthy gut suppressed the classical antiviral response and promoted an anti-inflammatory response. In contrast, viruses from the inflamed UC or CD gut strongly promoted the inflammatory state. Similar results were observed when the researchers isolated viruses from ileostomy fluid of IBD patients.

Viruses significantly elevated in IBD colonic tissue include caudovirales bacteriophages and enterovirus B, particularly echovirus serotypes. Fecal virome analysis misses eukaryotic enteroviruses as potential pathogenic agents in IBD.

To confirm the in vitro findings, the researchers reduced the gut virome of mice and introduced normal, UC-associated, or CD-associated human colon tissue viromes. Mice treated with the normal virome were protected from intestinal inflammation, whereas the IBD virome triggered inflammation and intestinal damage.

Similarly, in a mouse model of ulcerative colitis, transplantation of healthy human gut viral populations protected against inflammation and damage, whereas viral populations from IBD patients exacerbated tissue damage.

Recognition of viral communities by the host immune system is essential for their ability to confer immunity or contribute to disease. Therefore, the gut virome has autonomous immunomodulatory potential, similar to the microbiome.

Harnessing the gut's viral population is a potential approach to suppress inflammation in IBD. The MGH team plans to explore two strategies: targeted elimination of pathogenic viruses (such as with vaccines or antiviral drugs) and transplantation of viral populations isolated from healthy individuals, specifically from colon tissue.

The authors speculate that viruses may already play a role in successful fecal transplants to treat infections such as Clostridium difficile.

Fluctuations in the virome have also been reported in colorectal cancer, type 1 diabetes, nonalcoholic fatty liver disease, HIV infection, and other diseases, so therapeutic modulation of the virome may have broad implications.

Original link:
https://advances.massgeneral.org/digestive-health/journal.aspx?id=2280