The underlying cause behind the autoimmune response commonly seen in Type 1 diabetes (T1D) patients continues to be a mystery in medical research. Now, this might change. Boston College and Joslin Diabetes Center researchers have discovered a certain species of human gut bacteria that makes a peptide which mimics the specific insulin peptide targeted by the immune system in Type 1 diabetes.
Analysis has showed that the immune cells that target the involved insulin peptide react with the similar sequence from the peptide of the gut bacteria. In mice, there was a clear association with onset of T1D related to this. Since this type of diabetes is common in children, an important discovery was also that there’s a link between the gut bacteria and the development of T1D in children who are genetically predisposed to it.
“Although genetics and family history contribute to the risk of developing Type 1 diabetes, the incidence rate of Type 1 diabetes in children is rising at rates exceeding what can be explained on a genetic basis alone,” says C. Ronald Kahn, MD, Chief Academic Officer, Joslin Diabetes Center, in a statement. “Our findings suggest that exposure to a peptide made by gut bacteria that resembles an insulin peptide could stimulate or enhance the autoimmune response that initiates Type 1 diabetes.”
Kahn and team examined microbial databases, identifying 47 microbial peptides that matched the T1D-targeted insulin peptide by at least 50%, which is called the insB:9-23 peptide. They synthesized 17 of the most similar peptides and tested them for their ability to activate insB:9-23-specific immune cells unique to T1D. The scientists showed that only one of the selected peptides, from a gut bacterium called Parabacteriodes distasonis, was capable of triggering both human and mice immune cells specific to this peptide.
The researchers then showed that giving this gut bacterium to mice with a genetic risk for the disease resulted in more severe inflammation in the involved cells in the pancreas, as well as an earlier onset of diabetes. Analysis of human gut microbiome data from a study of 269 genetically predisposed infants, ages 0 to three years, showed that children who have this in their gut microbiome from a young age have a much higher risk of developing the disease compared to those without it.
The researchers believe that this new, gut-focused lens of viewing T1D may help to better develop prevention and intervention measures for this disease, and maybe other types of autoimmune disorders as well.
“A plethora of human gut microbiome studies have demonstrated that the composition of gut microbiota in patients with autoimmune diseases, including multiple sclerosis, inflammatory bowel disease and others, are significantly different from those in healthy controls,” says Kahn. “Our findings demonstrate a new link in which there is molecular mimicry between a peptide made by normal gut microbes and the autoimmune response in Type 1 diabetes. This suggests the potential to develop new tools, including vaccines, antibiotics or probiotics, for the prevention and treatment of Type 1 diabetes and perhaps other autoimmune diseases.”
This study is published in the journal Proceedings of the National Academy of Sciences.