In the largest longitudinal study of the microbiome to date, researchers from the Broad Institute of MIT and Harvard, Massachusetts General Hospital (MGH), and the DIABIMMUNE Study Group have identified a connection between changes in gut microbiota and the onset of type 1 diabetes. The study, which followed infants who were genetically predisposed to the condition, found that onset for those who developed the disease was preceded by a drop in microbial diversity — including a disproportional decrease in the number of species known to promote health in the gut.
These findings, published by Cell, Host & Microbe, could help pave the way for microbial-based diagnostic and therapeutic options for those with T1D.
The human microbiome, which consists of the trillions of microorganisms (bacteria, viruses, and other assorted “bugs”) that reside in our bodies, has become an area of growing interest to the medical community as researchers have begun to probe the role it plays in human health and disease. While most bugs in our microbiome are harmless, and even beneficial, changes in the microbiome (and in the interactions microbial species share with their human hosts) have been linked to various disease states, including diabetes and Inflammatory Bowel Disease.
To explore the possible connection between changes in the microbiome and type 1 diabetes, a team led by Ramnik Xavier, an Institute Member of the Broad and Chief of Gastroenterology at MGH, followed 33 infants (out of a much larger cohort of Finnish and Estonian children) who were genetically predisposed to T1D. From birth to age 3, the team regularly analyzed the subjects’ stool samples, collecting data on the composition of their gut microbiome.
In the handful that developed T1D during this period, the team observed a 25% drop in community diversity (in other words, in the number of distinct species present in the microbiome) one year prior to the onset of the disease. They also noted that this population shift included a decrease in bacteria known to help regulate health in the gut, along with an increase in potentially harmful bacteria that are known to promote inflammation. The findings are further evidence of a previously identified link between inflammation of the gut and type 1 diabetes.
“We know from previous human studies that changes in gut bacterial composition correlate with the early development of type 1 diabetes, and that the interactions between bacterial networks may be a contributing factor in why some people at risk for the disease develop type 1 diabetes and others don’t,” said Jessica Dunne, Director of Discovery Research at JDRF, which funded the study. “This is the first study to show how specific changes in the microbiome are affecting the progression to symptomatic T1D.”
Previous studies have shown that transferring microbiota from mice that were predisposed to autoimmune diabetes (the mouse equivalent of T1D) to mice that were not predisposed increased the prevalence of autoimmune diabetes in mice that were otherwise unlikely to develop the disease. Studies in humans have also shown an association between T1D and the bacterial composition of the gut. However, those studies were retrospective, meaning they were conducted after the patients developed the disease, making causality difficult to prove.