Type 1 Diabetes Risk May Come Down to Gut Bacteria Counts

A Joslin researcher describes experiments testing the hygiene hypothesis.



Diabetes researchers have long noticed that labs have different rates of success breeding mice to have the equivalent of Type 1 diabetes. At first, many scientists attributed this to poor management of genetic drift in some labs, but this theory didn’t hold up. If you transferred a group of mice from a lab with a lower rate of diabetes to a lab with a higher rate, the transferred group would soon exhibit the same rate of diabetes found in the new surroundings.

Some scientists decided to test whether the environmental conditions at the differing labs affected the rate of non-obese diabetes in the mice, according to Dr. Aleksander Kostic, an assistant investigator at Joslin Diabetes Center in Boston. They raised the mice in a completely sterile, germ-free environment, and found that the rate of non-obese diabetes quickly climbed upwards. They then transferred stool from mice raised in a non-sterile environment to mice raised in a sterile environment, and noticed that the rate of diabetes for the mice who received the transplanted stool went down.

“This seemed to indicate that a lack of exposure to microbes was somehow having a severely detrimental effect on the immune system and preventing protection from Type 1 diabetes to mice that were genetically prone,” Dr. Kostic said in a phone interview with Insulin Nation.

Findings like these have given rise to the hygiene hypothesis. This theory supposes that our immune systems are genetically designed to handle a certain load of exposure to microbes. As society’s hygiene has improved, it has left the immune system with not enough to do, the theory goes, and it becomes more prone to attacking the body. This could have led to a rise in autoimmune diseases like Type 1 diabetes.

With this theory in mind, Dr. Kostic and others have observed that gut bacteria becomes less diverse in people with Type 1 a year before diagnosis. The guts of people with Type 1 become dominated by several bacteria shortly before diagnosis, including some that can cause inflammation of the gut.

There are some obvious ethical hurdles to overcome before testing this theory on humans in a clinical trial, but history has provided some living laboratories where scientists have been able to observe it in practice. Dr. Kostic and other researchers collaborated with researchers in Finland, which has the highest rate of Type 1 diabetes in the world, and Russia. They focused on the Karelian region of Finland, which borders Russia. This area has a border that has been a moving target over the last century, and the people there are genetically similar on both sides. Since the Cold War began, however, Russian citizens have had a poorer standard of living than Finnish citizens, and this has exposed them to a higher and more diverse amount of microbes. That may be why Finnish children have a markedly higher rate of Type 1 diabetes, Dr. Kostic said.

Over several years, researchers collected samples of gut bacteria in this region from children who were determined to be genetically at risk of developing Type 1 diabetes. There was a big difference in the bacteria count of the two groups in the first year of life. The guts of Finnish children were dominated by a group of bacteria called bacteroides, a group which was largely absent in Russian children. The difference became less pronounced after the first year of life. This could mean that there is an important window of time when the guts of infants can be trained to shield from Type 1 diabetes.

“The data seems to suggest that a child needs to be exposed to these environmental organisms to alter their biohome in a specific way,” Dr. Kostic said.

So far, researchers have been successful in observing this phenomena, but they can’t yet explain why it occurs. That’s what Dr. Kostic and his team of researchers will now focus on next in a new phase of research. They will introduce various microbes into the non-obese diabetic mice to determine the exact relationship between microbe levels and risk of Type 1 diabetes. They hope then to develop possible microbial treatments that could be tested on humans. Their research also might rewrite the rule book on hygiene advice for parents of newborns. It’s too early to tell what might happen with this line of research, but Dr. Kostic is hopeful it will advance our understanding of why some children get Type 1 diabetes and other children avoid it.

”We don’t know where we’re going to be in five years, but I think we’re going to be much closer to understanding the mechanisms of what’s going on,” Dr. Kostic said.

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Craig Idlebrook is managing editor for Insulin Nation and Type 2 Nation. He's written about health policy, environmental health, community health, and maternal health for over 25 publications. You can reach him at cidlebrook@epscomm.com.