Article : Type 1 Diabetes Risk Linked to Intestinal Viruses


Viruses in the intestines may affect a person’s chance of developing type 1 diabetes, according to a study published in the Proceedings of the National Academy of Sciences (PNAS).

Children whose gut viral communities are less diverse are more likely to generate self-destructive antibodies that can lead to type 1 diabetes.

In addition, children who carried a specific virus belonging to the Circoviridae family were less likely to head down the path toward diabetes than those who carried members of a different group of viruses.

“We identified one virus that was significantly associated with reduced risk, and another group of viruses that was associated with increased risk of developing antibodies against the children’s own cells,” said senior author Herbert “Skip” Virgin IV, MD, Washington University School of Medicine, St. Louis, Missouri. “It looks like the balance of these 2 groups of viruses may control the risk of developing the antibodies that can lead to type 1 diabetes.”

The findings suggest a way to predict, and maybe even prevent, the life-altering diagnosis.

The new research follows an earlier study by Mikael Knip, MD, University of Helsinki, Helsinki, Finland, and Ramnik Xavier, MD, Massachusetts General Hospital, Boston, Massachusetts, who studied the gut bacterial ecosystems of 33 children who carried genes that put them at high risk of developing type 1 diabetes. The researchers collected monthly stool samples from the children from birth to age 3, and monitored the children for the development of auto-antibodies and the disease. In a small group of children who developed type 1 diabetes, the team noted significant alterations in the diversity of bacterial species in the gut before diagnosis. However, the study only looked at bacteria in the gut, not viruses.

For the current study, the researchers took the same samples and analysed the population of viruses in a select subset of children. They carefully matched 11 children who went on to acquire auto-antibodies -- 5 of whom later developed type 1 diabetes -- with 11 children who did not develop auto-antibodies or the disease. All 22 children carried genes that put them at high risk to develop the disease.

A previously unknown virus related to circoviruses was found in 5 of the 11 children who did not develop auto-antibodies, but not in any of the children who did.

“Circoviruses have never been associated with disease in people,” said first author Guoyan Zhao, PhD, Washington University School of Medicine. “Multiple lines of evidence support the inverse association between the virus we found and the development of auto-antibodies. This suggests that having a circovirus may be a good thing for people at high risk for diabetes.”

The researchers also found that children carrying bacteriophages that target Bacteroides species were more likely to start down the path toward diabetes.

“Previous studies had found that changes in Bacteroides species are associated with developing type 1 diabetes, and here we found that viruses that infect Bacteroides are associated with the development of auto-antibodies,” said Dr. Virgin. “Our findings support the idea that Bacteroides or other bacteria, and the viruses that infect them, play a role in the pathological process that leads to diabetes.”

When each child’s gut viral population was analysed as a whole, the researchers found that children who went on to take a first step toward diabetes had fewer and a narrower range of viruses than those who did not.

“There are many autoimmune diseases that are much more common these days,” said Dr. Virgin. “It could be that we’ve made ourselves unhealthy by not having the right viruses in our virome.”

“There’s a lot of verification that needs to be done,” he added. “We need to see if we can replicate these findings in another group of children, and then we have to show causality in an animal model. But if these results hold up, we may one day be able to prevent type 1 diabetes by treating high-risk children with circoviruses. It can be a terrible disease and no one knows how to prevent it. Circoviruses are worth investigating.”

SOURCE: Washington University in St. Louis