Changes in Child’s Microbiome Linked to Type 1 Diabetes Development, According to Study Led by OU Health Harold Hamm Diabetes Center

       A research team led by Jed Friedman, Ph.D., director of OU Health Harold Hamm Diabetes Center at the University of Oklahoma Health Sciences Center, and Chongle Pan, Ph.D., associate professor of computer science and microbiology on OU’s Norman campus, has published a study in the journal Nature Communications showing that the development of Type 1 diabetes is linked to shifts in the microbiome of a child.

      “The microbiome of the intestinal tract is a new frontier in research because of the insight it is yielding about healthy functioning as well as the development of disease,” Friedman said. “The microbiome, which is a collection of trillions of microorganisms, is of particular interest to diabetes researchers because children derive their first microbiomes from their mothers. From that foundation, babies continue developing their microbiomes with influences from breast milk, environmental exposures, ongoing nutrition and other factors.”

      During this time, known as the first 1,000 days, the microbiome influences the development, structure and function of organs such as the liver, pancreas and brain. One of the critical pathways in which this occurs is through the immune system. Because the microbiome essentially educates cells about how to function, particularly the immune system, the establishment of a healthy, balanced microbiome is vital. Disruption of the microbiome may cause long-term effects on systems like the immune system, which is key in the development of Type 1 diabetes.

      In this project, the research team analyzed 887 children from infancy to age 3 who were at high genetic risk for developing Type 1 diabetes. If the children began producing autoantibodies against their pancreas, the researchers wanted to see whether that event corresponded with a change in their microbiomes. That’s exactly what they found — a distinct set of microorganisms were associated with the autoimmune reaction that progressively attacks and destroys insulin-producing cells. The finding is an important step toward stopping the development of Type 1 diabetes.

      “Knowing which microbes are associated with the conversion to autoimmunity, in which the immune system begins destroying cells in the pancreas, opens the door to interrupting that process,” Friedman said.

      The next stage in this research is to test modifications to the microbiome that potentially can stop the development of Type 1 diabetes in an animal model so that researchers can more quickly identify the proper strategy. Conducting studies in a preclinical model is a crucial phase before testing a potential therapy in humans.

      Studies of the microbiome are a major part of the research focus at Harold Hamm Diabetes Center. One of the center’s three pathways toward a cure for diabetes is the “first 1,000 days” — from conception to a child’s second year of life. During that time, there are critical windows of development, like that of the microbiome, that affect a person’s health across the life span.

      Children whose microbiomes were analyzed were part of the TEDDY (The Environmental Determinants of Diabetes in the Young) study and had either a genetic predisposition for Type 1 diabetes or a first-degree relative with the condition. Participants represented a wide geographic area, including the United States, Germany, Sweden and Finland.

      Other members of the research team were Harold Hamm Diabetes Center researchers Karen Jonscher, Ph.D., and Li Zhang, Ph.D. They were joined by several researchers on OU’s Norman campus as well as a collaborator at Oregon State University.

      The study can be found at www.nature.com/articles/s41467-022-31227-1.