Gut Microbes Protect Against Type 1 Diabetes in Mice

Research in mice has found that the trillions of bacteria and other microbes that live in the gut can blunt the immune system attack that causes type 1 diabetes. The discovery may shed light on rising rates of type 1 diabetes in developed countries.

Type 1 diabetes is an autoimmune disease in which the body's own immune system attacks and destroys insulin-producing beta cells in the pancreas. Type 1 diabetes accounts for about 5-10% of diagnosed diabetes in the United States. It develops most often in children and young adults but can appear at any age. People who have type 1 diabetes must take insulin daily to survive.

Scientists don't know exactly what triggers the body's immune attack on beta cells. A research team led by Alexander Chervonsky at the University of Chicago saw clues in the increased incidence of type 1 diabetes in developed countries during the past decades. The investigators suspected that changes in the environment, including the microbes that live in our bodies, may be influencing the disease. Supporting this idea, previous studies found that the incidence of type 1 diabetes in non-obese mice susceptible to diabetes can be affected by microbes in their environment. The researchers—funded by NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of Allergy and Infectious Diseases (NIAID), among others—set out to further explore the possible connection between type 1 diabetes and microbes.

Receptors on certain immune cells recognize molecular patterns that mark the surface of microbes. These immune cells signal through a protein called MyD88 to launch an immune system response. In the September 21, 2008, online edition of Nature, the researchers explained that, when they disrupted the gene for MyD88 in non-obese diabetic mice that were susceptible to diabetes, the mice no longer developed type 1 diabetes.

While the researchers confirmed that immune activation in the MyD88-deficient mice was suppressed in pancreatic lymph nodes, it wasn't eliminated. Thus, type 1 diabetes prevention was likely more than simply a matter of turning off part of the immune system. The researchers therefore raised the mice germ-free. These same mice developed type 1 diabetes when raised in a germ-free environment, showing that the disease isn't dependent solely on the MyD88 pathway.

The researchers next gave the germ-free mice a defined mix of “friendly“ gut bacteria and found that the incidence of diabetes was significantly reduced. These experiments show that a complex interaction between the immune system and bacteria in the gut may help to lower the risk of developing type 1 diabetes.

The widespread use of antibiotics and more aggressive cleanliness of modern society can alter the mix of microbes living in our body. This research suggests that an unintended consequence of this change is an increased risk of autoimmune diseases like type 1 diabetes. The idea needs to be further explored, but it hints at the possibility of developing bacteria-based treatments for people with autoimmune diseases.

—by Harrison Wein, Ph.D.