An international research team has uncovered compelling evidence that gut-microbe-derived molecules may play an important role in shaping the developing immune system during early childhood. The findings provide a new perspective into how early gut microbiome development may contribute to the risk of autoimmune diseases, including type 1 diabetes.

The study analysed more than 300 stool samples collected from children between 3 and 36 months of age. These children carried a genetic risk for type 1 diabetes, and some went on to develop islet autoantibodies, early markers of the disease. Researchers tracked over 100 microbially conjugated bile acids, a class of compounds that were only recently discovered and remain poorly understood.

Bile acids are made from cholesterol in liver and secreted after every meal in the intestine to help digest fat. Scientists have only recently learned that bacteria in our intestine can recombine them with different amino acids as well as other molecules, producing a vast range of new bile acid structures. These microbially produced molecules were long overlooked and were discovered only within the past few years.

“This is the first study to show how these gut-microbe-derived bile acids develop during the first years of life,” notes Professor and principal investigator Matej Orešič from Örebro University in Sweden and the University of Turku in Finland.
The research indicates that as children grew, liver-derived primary bile acid conjugates declined, while gut-microbe-derived secondary bile acid conjugates steadily increased.

Gut chemical profile links to signs of type 1 diabetes

Several of these bile acids differed significantly in children who went on to develop one or more islet autoantibodies when compared with children who remained autoantibody-negative. The study showed that the infants who developed islet autoantibodies had altered levels of certain bile acid conjugates, such as deoxycholic acid conjugates and ursodeoxycholic acid conjugates. This suggests an imbalance in how the gut microbes co-produce these compounds.

The researchers also identified specific gut bacteria whose abundance was strongly linked with these bile acid patterns.

“This fits with currently emerging evidence that bile acids are key to gut microbiome and immune maturation during early life,” points Academy Research Fellow Santosh Lamichhane from the University of Turku.

Because type 1 diabetes is an immune-mediated disease, the team also tested whether these newly identified bile acids could influence human immune cells. In laboratory assays, several microbially conjugated bile acids were found to modulate inflammatory signaling in monocytes, including responses to lipopolysaccharide, a potent immune stimulant derived from bacteria. Some bile acids dampened inflammatory pathways, while others amplified them.

Additionally, the scientists showed that the microbially-conjugated bile acids could directly affect the differentiation of Th17 cells and regulatory T cells (Tregs), two immune cell types that help balance inflammation and immune tolerance.

Toward early-life prevention strategies

Together, the findings reveal a new and previously unrecognized layer of microbiome–immune communication occurring at a critical phase in childhood when the immune system is still being trained.

“Our work highlights how newly discovered microbially-modified bile acids may shape immune development during infancy,” Orešič explains and continues:

“These molecules vary with age, link closely to specific gut microbes, and directly regulate immune and inflammatory responses. This may help explain why disturbances in early-life microbiome development are associated with higher risk of autoimmune diseases, including type 1 diabetes.”
While more research is needed to determine causality, the findings raise the possibility that microbially-conjugated bile acid profiles could one day help identify children at higher risk, or even point toward new early-life interventions that support a healthier immune trajectory. This research, published in prestigious Nature Communications journal, is part of the EU project INITIALISE, which is coordinated by Orešič and supported by the Research Council of Finland.