by Elise Wachspress
In September 2008, Nature published a feature story hailing the work of Alexander Chervonsky, PhD, and his team at the University of Chicago. They had recently found startling evidence that the microbiome—the complex community of trillions of microbes living in our guts, skin, and elsewhere—could provide an explanation for rising rates of type 1 diabetes, particularly in developed countries.
While there is clearly a genetic component to the disease, the team knew there must be other factors at work, since genetic change in human populations just doesn’t happen that quickly.
Chervonsky’s team hypothesized that a protein named MyD88, which regulates immune responses to resident microbes, was a player. So they genetically engineered mice prone to type 1 diabetes but without the gene that encoded MyD88.
None of these “knock-out” mice developed the disease. But, amazingly, when the knock-out mice were raised in an environment without bacteria, they did.
And when Chervonsky’s team looked more closely at mice with the MyD88 gene, they realized the microbiome of those mice was actually different than the knock-out mice. The MyD88 gene was actually tilting the balance of the gut microbial composition to promote diabetes.
Clearly, the combination of gut microbes and the gene MyD88 was somehow involved in type 1 diabetes. And these effects were being felt in the pancreas, not in the gut, where the microbes lived. What were the mechanisms that caused these outcomes? Follow-up studies in Chervonsky lab suggested that a combination of the mice’s genetic makeup and the composition of the microbiota in their environment could shift the balance from health to disease.
Opening a whole new area of science
The “ecosystems” we inhabit include not only plants and animals, air and water. We are profoundly affected by the trillions of microbes living in, on, and around us as well. We may not be able to see them, but our genomes have been co-evolving with these tiny organisms for millennia—and they may be powerful agents in maximizing our health and well-being, protecting us against disease as well as occasionally causing it.
Thanks in part to basic research by Chervonsky and his team, there has been an explosion of studies linking the microbiome and type 1 diabetes. JDRF, the leading global organization focused on type 1 diabetes research, has reoriented significant funding toward microbial approaches. Recently, large longitudinal studies on babies—humans, not mice—show that a drop in microbial diversity seems consistently to precede development of the disease.
By looking closely at the stool samples of babies like these, we may discover the bacterial mix that can keep others from developing disease. Perhaps introducing these bacteria to babies at risk could assure they remain free of type 1 diabetes—an onerous, life-long condition that requires constant monitoring, and infusion or injections of insulin strictly balanced with eating and exercise. Or what if we isolate the protective bacterial by-products and add to infant formula or yogurt?
Getting safely to effective clinical applications is not a simple process; the ethical considerations alone are far more complex than any work with baby mice. But the current costs exacted by type 1 diabetes—in medical care, lost school and work time, and most importantly, quality of life—make investing in this avenue of discovery as valuable as, say, new surgical techniques.
The Duchossois Family Institute: Harnessing the Microbiome and Immunity for Human Health, is founded on that premise: that understanding how these two forces—the microbiome and immunity— work together can yield a new foundation for robust, life-long wellness. Baked into the Institute’s plan are advanced data collection and computational analysis and the business strategies that can accelerate breakthroughs like those made by Chervonsky’s team. The DFI will start from basic science research like his—absolutely essential to understanding biological systems—and move findings rapidly to clinical application and the commercialization that makes these accessible to many around the world.
We hope you will be a frequent visitor to this blog as we demonstrate growing understanding of the role of the microbiome in allergy, Alzheimer’s, hypertension, obesity, cancer, celiac disease, sleep, lung conditions, neurodevelopmental conditions, and more.
Join us for what we believe will be an amazing journey.
Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office
