What is the Role of Gut Bacteria on Developing T1D?

A pair of new studies published today are aiming to help answer that question.

Both studies are from the TEDDY study.  TEDDY – which stands for The Environmental Determinants of Diabetes in the Young – is an international study tracking thousands of babies at high genetic risk of type 1 diabetes (T1D). The aim is to determine which individuals develop T1D, to spot patterns that point us toward potential triggers for the condition.

In these two studies, children were enrolled at birth and followed for the development of islet autoimmunity and T1D.  Stool samples were collected and analyzed both for their bacterial content and to gain an understanding of how the bacteria function.

JDRF has had a long history of supporting TEDDY, and both current studies were partially funded by JDRF.

Why did they do this research?

We know that certain genes can make people more likely to develop T1D, but scientists have long suspected that something in the environment is triggering the condition to develop.  The rising incidence of T1D over the past few decades suggests that these environmental factors may be playing an increased role in T1D development. The gut microbiome is one such factor.

Previous research suggested that gut bacteria may play a role in T1D, but TEDDY is the largest study to date to look at this question.

What did they do?

Over 700 children at genetic risk of T1D took part in these two studies. The team collected stool samples every month from the age of three months until the age of four years and then every 3-6 months afterwards. The researchers observed whether each child the early stages of T1D.

The researchers then analyzed all the samples to see what kinds of bacteria were present, as well as the function of those bacteria in the body. They then determined whether that function was linked to factors such as how the children were born, whether they were breast-fed, and the presence of siblings and pets.

What did they find?

One study looked at the maturation of the gut microbiome in early life and found that there are three main phases that occur as gut bacteria communities develop in children. The development of these gut bacteria communities is linked to breast-feeding, birth mode, and living with siblings and furry pets, although there appeared to be only minor associations between gut bacteria and the onset of T1D.

The second study focused on identifying the function of the bacteria in the gut.  In kids who didn’t go on to develop T1D, there was an increase in the genes that produce a group of molecules known as short-chain fatty acids. This suggests that these short-chain fatty acids may help protect against T1D.  Furthermore, they found that human milk is one of the main factors contributing to the functional composition of the gut, suggesting another route for microbiome-based interventions.

What does this mean for type 1 diabetes?

These studies support earlier JDRF-supported research on the importance of the gut microbiome in the development of T1D, including previous work on the protective effect of short-chain fatty acids.

The current studies provide several avenues for further testing of the role of the gut bacteria in T1D.  They provide further evidence that the mechanisms of early-life microbiome and the subsequent effect on immune development and function will be critical to understanding how microbiome-based therapies can be tailored to prevent or delay the onset of T1D.

“These studies found some interesting changes to patterns of gut bacteria development in early childhood. But the relationship between gut bacteria, genetics and type 1 diabetes risk is still a complicated picture,” said Jessica Dunne, Ph.D., the lead of the JDRF Prevention Program. “We will need to carry out more research to work out how exactly factors affected by gut bacteria may be able to affect the risk of developing type 1 diabetes, and how we can exploit these factors to ultimately use the gut microbiome to prevent or delay progression.”