Immune responses to gut bacteria linked to onset of type one diabetes

Immune responses against common intestinal bacteria may help predict who will develop type one diabetes (T1D) and respond to a new immunotherapy, finds research from The Hospital for Sick Children (SickKids). 

As the incidence of T1D rises, researchers have wondered how a modern environment might be increasing the risk of developing the condition. One way of tracking environmental influences is through an examination of gut “microbiomes” – the microbial communities in people’s intestines. 

A research team led by Dr. Jayne Danska, a Senior Scientist in the Genetics and Genome Biology program, has uncovered a deeper understanding of what role the gut microbiome plays in the immune system of children at risk for T1D. Published in Science Translational Medicine, the study suggests that immune responses to gut bacteria may help identify who can benefit more from particular T1D treatments and when those treatments are most effective.   

“Not all individuals with a genetic risk for T1D, or even those with pre-diabetic features, will develop the condition,” explains Danska, who is also the Associate Chief of Faculty Development and Diversity at SickKids Research Institute. “Knowing this, we want to use medical interventions in individuals most likely to benefit from the treatments.” 

A new approach to T1D research 

In previous T1D research, genome sequencing of bacteria in the gut microbiome helped scientists make connections to some genetic risk factors associated with developing T1D. What was not identified until now, however, was a relationship between particular types of bacteria and future development of T1D.  

To help close this gap – and unique to this research – the study included people who were not yet diabetic. In examining blood samples from pre-diabetic participants, Danska’s team identified patterns in the abundance and types of antibodies that bound to certain bacterial species.  

Of the patterns noted, antibody responses to three different types of bacteria were predictive of the time to diabetes diagnosis and two of these were also associated with the effectiveness of teplizumab – an immunotherapy recently approved for use in the USA to delay the onset of T1D.  

Gut bacteria inform precision medicine 

Danska’s research suggests that antibodies against specific bacterial species are associated with time to future diabetes diagnosis and will help pave the way for Precision Child Health – a movement to deliver individualized care to every patient

“Our findings exemplify what is meant by research to advance precision medicine,” Danska says. “In the future, an individual’s immune response to the microbiome can inform choices of treatment to protect them from T1D when they display evidence of risk for the condition.” 

Pro-active screening and personalized approaches to diabetes prediction, prevention and treatment may improve outcomes for children with the condition. Earlier this year, two SickKids research projects led by Drs. Diane Wherrett and Farid Mahmud were awarded more than $15 million in funding from the Canadian Institutes of Health Research (CIHR) to improve outcomes for children with diabetes. 

This research was funded by Canadian Institutes of Health Research (CIHR), the Juvenile Diabetes Research Foundation (JDFR), the National Institutes of Health (NIH), the Anne and Max Tanenbaum Chair in Molecular Medicine and SickKids Foundation.