Abundance of Enteroviruses in the Gut Linked to Type 1 Diabetes Precursor
Although the cause of childhood-onset type 1 diabetes remains unknown, a new study links a precursor of the condition to an abundance of certain viruses in the gut.
A new study by Columbia University's Mailman School of Public Health investigators has added new findings on the link between the presence of enteroviruses in children’s intestinal tracts and the onset of islet autoimmunity, which leads to type 1 diabetes.
Nonpolio enteroviruses made the news in 2018 after 1 enterovirus was linked to an outbreak of acute flaccid myelitis in Colorado children. Although enteroviruses can also cause illnesses such as hand, foot, and mouth disease, the recent study published in the journal Scientific Reports adds to the evidence linking these viruses to childhood-onset type 1 diabetes, once known as juvenile diabetes. According to the US Centers for Disease Control and Prevention (CDC), there are nearly 18,000 children and adolescents younger than 20 years diagnosed with type 1 diabetes annually.
There is currently no known way to prevent type 1 diabetes. In an interview with Contagion®, study author Thomas Briese, PhD, associate professor of epidemiology at the Columbia University Medical Center, explained why the cause of the condition is so mysterious.
“Type 1 diabetes results from a complex interplay of genetic predisposition, immunologic capability, and environmental triggers. Even in monozygotic twins, one sees divergent outcomes,” said Dr. Briese. “This shows that genetic background alone is not sufficient for type 1 diabetes and stresses the importance of environmental factors, including nutrition, hygiene, geography, and virus infections.”
In the study, investigators characterized the virome of 93 Australian children—45 of whom had the type 1 diabetes precursor islet autoimmunity and 48 matched controls—using blood and feces samples. The children were part of a prospective birth cohort, known as the Australian Viruses in the Genetically at Risk study, with at least 1 first-degree relative with type 1 diabetes. Using a viral sequencing tool that is up to 10,000 times more powerful at identifying viruses than conventional sequencing methods, the study team identified 129 viruses in the fecal samples that were more abundant in the guts of children with islet autoimmunity compared with age and gender-matched controls. Among those, there were 5 enterovirus-A viruses, which investigators found to be significantly more abundant in some cases.
“During an infection, enteroviruses are commonly shed in stool for 3 to 4 weeks, though can go upwards of 3 months in rare cases. The efficiency of an individual’s immune response contributes to this variance, as more efficient responses help to eliminate the virus faster,” explained Dr. Briese. Enteroviruses that spread to a child's pancreas can trigger autoimmunity in cells that regulate blood sugar, the findings indicate.
“Viruses in the gut are only part of the issue,” added Dr. Briese. “Another factor is how the viruses may affect pancreatic islets and their function. Enteroviruses have been found in islet beta-cells and were shown to have damaged genomes preventing their usual rapid multiplication so that they are trapped in the cells. The presence of these persisting viruses in the pancreas is considered to provide one of the mechanisms triggering autoimmunity, beta-cell destruction, and ultimately [type 1 diabetes].”
Dr. Briese noted that the next step in the team’s research will be to extend their current analyses to larger numbers of samples and confirm the initial findings. “While it is challenging to identify the reason why type 1 diabetes develops in some people and not others, more data from prospective cohort studies like ours will help refine our findings and identify the possible differences in reactions to enterovirus infection.”