The onset of type 1 diabetes is mysterious, but one thing is for sure: some environmental factor triggers the immune system attack on beta cells. This environmental trigger is a longstanding mystery that research at Joslin Diabetes Center is beginning to unravel. Aleksandar D. Kostic, Ph.D., is studying how the communities of bacteria that line our digestive systems, also known as the microbiome, could start a chain reaction that leads to autoimmunity and type 1 diabetes.
“The gut is the largest immune organ in the body,” says Dr. Kostic. “It plays an important role in distinguishing self from non-self, distinguishing all of our symbiotic bacteria from pathogens and food antigens and [many other] exposures.” These things develop the immune system by helping it to learn what to fight and what to leave alone.
People who are genetically prone to type 1 diabetes already have compromised immune systems. Their immune cells think beta cells are like viruses, dangerous invaders that need to be destroyed. These rogue immune cells can be kept under control by the rest of immune system if the bacteria in the gut of someone with a healthy, well-balanced microbiome works together with the immune system to protect against disease. But if the microbial balance gets thrown out of whack it could inflame the gut. This inflammation could trigger a massive immune response throughout the body, overwhelming the system’s ability to keep the beta cell autoimmunity in check, freeing those rogue immune cells to attack and destroy beta cells.
To test this hypothesis, Dr. Kostic will be working with a germ-free isolator, specialized housing for the mice that allows researchers to control the presence of bacteria and fungi to create a strain of mice without microbiomes. Joslin’s germ-free facility is the first in the country to be solely devoted to diabetes research.
Based on observations from his previous microbiome experiments, Dr. Kostic plans to transplant microbiomes isolated from people with varying stages of type 1 diabetes into the mice. He will then watch how the immune system changes along with the microbiome and how that relates to immune cell attack in the pancreas.
The germ-free aspect of this experiment is important. “You can’t just take a conventional mouse that already has a complex microbiome and introduce another microbiome to that mouse because the resident microbiome is very entrenched and is going to prevent colonization by almost all new bacteria,” he says. “So that’s why these kind of experiments can only be done with a clean slate, where you start with a mouse without any microbes.”
Dr. Kostic hopes that this research will help to uncover the elusive environmental trigger of type 1 diabetes. “Once we have a set of these correlated events between the microbiome and the immune system, we can start digging into them in more detail,” he says. “If we can identify what they are, [we could] try to eradicate them, or if there are certain [preventative] aspects of the healthy microbiome we want to supplement with those to prevent diabetes.”
Check back on Thursday for part 2 of this story, about the observations and experiments leading up to Dr. Kostic’s work at Joslin.