Boston – The intestinal bacterium Parabacteroides distasonis, a component of the intestinal flora, could be the trigger for the autoimmune reaction that leads to the formation of insulin antibodies in the first few years of life, which later destroy the beta cells and trigger type 1 diabetes. This is reported by US researchers in the Proceedings of the National Academy of Sciences (PNAS 2022; DOI: 10.1073/pnas.2120028119).
It has long been known that type 1 diabetes is an autoimmune disease and that insulin antibodies play a key role in it. However, what causes the immune system to form the autoantibodies was unclear.
Intestinal bacteria have long been suspected of being the trigger. The immune system closely monitors the development of the microbiome in the first years of life and, if necessary, forms antibodies to prevent the bacteria or other microbiota from spreading to the body.
According to the theory of molecular mimicry, antibodies could accidentally be created that attack the body’s own structures if they happen to have the same epitopes as the bacteria.
A team led by Ronald Kahn from the Joslin Diabetes Center in Boston has systematically searched for the responsible antigen. The search was for a section “insB:9-23” of the insulin molecule, which is a frequent target of autoantibodies in type 1 diabetes.
They found a total of 17 proteins that matched “insB:9-23” more than 50%. One of the proteins, “hprt4-18”, found in the intestinal bacterium Parabacteroides distasonis, was able to activate the T cells of patients with type 1 diabetes and non-obese diabetic (NOD) mice in laboratory tests.
The NOD mice are a model of the disease in humans. When the researchers infected the animals’ intestines with P. distasonis, there was an increased inflammatory response in the islet cells and an earlier onset of type 1 diabetes.
Finally, the researchers examined stool samples from 269 children who are at increased risk of type 1 diabetes and who are regularly examined in the DIABIMMUNE longitudinal study. In fact, children whose stool samples had the “hprt4-18” peptide detectable developed the autoantibodies that are the first sign of impending type 1 diabetes much more frequently. © rme/aerzteblatt.de