Gut microbiome maturation linked to children’s risk of type 1 diabetes, study finds

US-based researchers identify the gut microbiome’s role as a potential indicator of type 1 diabetes in children, a disease affecting more than nine million people globally. The new study looked beyond the known genetic aspects of the disease, turning to environmental factors, including the microorganisms’ development in the gut. 

The investigators found that children with an early stagnated gut microbiome were three times more likely to develop type 1 diabetes compared with those with a continuously maturing microbiome. Genetics also played a role in how strong this correlation was.

“The disease burden of type 1 diabetes is substantial for children and their families, requiring careful management of insulin, exercise, and diet from a very early age,” says co-author Daniel Wang, Sc.D., associate scientist with the Channing Division of Network Medicine in the Mass General Brigham Department of Medicine. 

“Understanding the role of microbiome development in diabetes progression could lead to early prediction and prevention strategies, giving us more options to delay or even prevent the clinical manifestation of this disease.” 

Investigating maturation patterns

Published in Nature Metabolism, the study included 887 children from Germany, Sweden, Finland, and the US, all at high risk of developing type 1 diabetes. The research team analyzed over 12,000 stool samples during their first six years of life to track gut microbiome maturation.

The researchers identified three maturational patterns for the gut microbiome: early-maturing, late-maturing, and early-plateaued.The researchers explain that in type 1 diabetes, the immune system starts attacking insulin-producing cells years before any symptoms appear. The children were considered to have developed the disease at the point when the blood tests detected this attack or when they had received a diagnosis.

They also identified three maturational patterns for the gut microbiome: early-maturing, late-maturing, and early-plateaued. 

The children with an early-maturing gut microbiome had a rich and diverse population of gut bacteria already in the first year of life. In contrast, for those with a late-maturing microbiome, the development of this diversity was slower, as the researchers observed fewer changes and less diversity after one year.

Meanwhile, the children who had an early-plateaued microbiome had a slow-starting gut microbiome, but it never caught up. The researchers explain that their bacterial diversity was low for their first three years of life. 

The early-plateaued group had a three times higher risk of developing type 1 diabetes, or the immune attack preceding it, the researchers stress.

Biology of the microbiome

The research team was also interested in the biology of the microbiome and the influence of genetics. 

They explain that patterns of microbiome maturity also reflect what the bacteria are capable of doing. The study details that children whose microbiome matured early did the shift earlier from having milk-adapted bacteria such as Bifidobacterium toward having species that break down dietary fiber — a sign that the child is ready for a more varied diet. 

The research team was also interested in the biology of the microbiome and the influence of genetics.Meanwhile, the children with the earlier plateaued microbiome mainly digested milk sugars even if solid foods had been introduced.

“Genetic background can change how much a given maturation pattern matters for risk, so combining microbiome and genetic information gives a more accurate picture,” says lead author Danyue Dong, Ph.D., a postdoctoral research fellow in the Channing Division of Network Medicine at Mass General Brigham. 

“By analyzing interactions between the microbiome and host genetics, we found genetic variants, particularly those involved in antimicrobial and antiviral immune responses, that shaped how strongly the late-matured pattern was related to disease risk. The early-plateaued pattern, by contrast, carried a higher risk regardless of genetic background.” 

The study cannot determine cause and effect, yet the authors argue that the findings provide evidence of a link between the gut microbiome development and type 1 diabetes. They stress the need for future studies to do similar testing on children who are not at high risk of type 1 diabetes, to see if the findings can be applied to the general population. 

Previous studies have also investigated the link between the gut microbiome and metabolic health. Researchers discovered metabolites that impact liver metabolism and insulin sensitivity, traveling from the intestine to the liver and then to the heart, from where they are spread to the rest of the body. This finding may have potential applications in future treatments for obesity and type 2 diabetes, the authors argued.