Intestinal Viruses Appear to Correlate with T1D Risk

The viruses in a child’s intestines may hold clues about how likely the child is to eventually develop type 1 diabetes (T1D), according to a new study.

Scientists from Washington University in St. Louis say children with less diverse intestinal viromes are more likely to be diagnosed with T1D.

Herbert “Skip” Virgin IV, MD, PhD, said he and his team also found correlations between specific groups of viruses and the risk of T1D.

“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 Virgin, a professor and head of pathology and immunology at the university. “It looks like the balance of these two groups of viruses may control the risk of developing the antibodies that can lead to type 1 diabetes.”

The research is potentially significant because doctors currently have no way to accurately predict which children are at the highest risk for T1D, aside from genetic risk factors.

According to the Juvenile Diabetes Research Foundation, about 40,000 US children are diagnosed with T1D each year.

In hopes of getting a better understanding of T1D risk, the researchers collected 220 virus-enriched preparations from fecal samples of 22 children who had genetic risk factors for developing T1D. Of those children, half had developed the autoantibodies associated with the inhibition of insulin production, and 5 of those 11 were diagnosed with clinical T1D. The other children in the study had genetic risk factors but did not develop the T1D-associated autoantibodies.

By analyzing the fecal samples, researchers were able to draw distinctions between the viromes of children with T1D and those who did not get the disease despite their higher genetic risk profiles. The team also found a previously unidentified circovirus that appears to have a negative correlation with T1D risk. Five of the 11 children who did not develop the autoantibodies had the circovirus in their fecal samples, but none of the 11 children with the antibodies carried the virus.

Guoyan Zhao, PhD, an assistant professor of pathology and immunology at Washington University, said this could mark the first time a circovirus has been linked to a disease in humans.

“Circoviruses have never been associated with disease in people,” said Zhao, in a press release. “Multiple lines of evidence support the inverse association between the virus we found and the development of autoantibodies. This suggests that having a circovirus may be a good thing for people at high risk for diabetes.”

Conversely, the researchers found that children whose viromes contained bacteriophages that target Bacteroides—a group of intestinal bacteria—were at a higher risk of developing T1D.

“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,” Virgin said. “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.”

The Washington University study follows a 2015 study in Finland which looked at the gut microbiomes of children with high T1D risk and found similar correlations between bacteria profiles and likelihood of developing T1D.

Virgin hopes his research and will not only lead to better prediction of T1D, but also eventually to prevention of the disease.

“There’s a lot of verification that needs to be done,” Virgin said. “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.”

The study, titled, “Intestinal virome changes precede autoimmunity in type 1 diabetes-susceptible children,” was published July 10 in PNAS.

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