Allergies and asthma affect an increasing number of children worldwide, but now an international research group led by DTU has identified a previously unknown mechanism that can reduce the risk of allergies and asthma later in life. The study shows that children are less likely to develop these diseases if, as infants, they are colonized with certain bifidobacteria that produce a substance in the gut - a so-called metabolite - that dampens immune responses to allergens.
The study, “Early-life colonisation by aromatic lactate–producing bifidobacteria lowers the risk of allergic sensitization,” has been published in the renowned journal Nature Microbiology.
The results could have a major impact on the prevention of allergies and asthma, which are among the most common chronic diseases in children. Being able to prevent them by strengthening the gut microbiota in the first months of life could be a breakthrough in public health.
"The key breakthrough is that we have now identified a specific mechanism that can suppress the development of allergic reactions in the immune system already during infancy. If we can translate this knowledge into a preventive strategy - for example, through probiotic supplements or enriched infant formula—it will be a major step forward in the fight against allergies and asthma, which currently affect millions of children worldwide," says project leader Susanne Brix Pedersen, professor at DTU Bioengineering.
Bacterial substance dampens allergic reaction
The researchers followed 147 children from birth to age five and found that infants who have a large population of certain bifidobacteria in their intestines early on benefit from the metabolites produced by these bacteria. In particular, the substance 4-hydroxyphenyl lactate (4-OH-PLA) appears to suppress the immune system's tendency to overreact to allergens.
In laboratory tests with human immune cells, the researchers demonstrated that 4-OH-PLA inhibits the body's immune system's production of the antibody immunoglobulin E (IgE), which plays a central role in allergic reactions. IgE is the body's “alarm molecule” in allergies. When the body encounters an allergen, it produces IgE antibodies, which activate immune cells and can trigger allergic symptoms. This happens because the IgE antibody binds to allergens such as pollen or food proteins, triggering the body's immune response and causing symptoms such as itching, eczema, hay fever, and in some cases asthma. The higher the IgE level, the greater the risk of allergy.
Laboratory tests showed that natural concentrations of 4-OH-PLA reduce the body's production of the IgE antibody by 60 percent without affecting the production of other types of antibodies.
Genetic analysis of stool samples
The study included large amounts of data from three large birth cohorts in Sweden, Germany, and Australia. The researchers analyzed stool samples from infants using, among other methods, genetic analyses and analyses of small molecules to map both bacterial composition and metabolite levels. At the same time, blood samples were used to measure IgE antibodies against food and airborne allergens. Finally, the mechanism was tested in an experiment with human immune cells, where 4-OH-PLA directly inhibited IgE production.
The study demonstrates a concrete biological link between certain bifidobacteria, the metabolites they produce, and a healthy development of the immune system in young children.
New strategy for preventing allergies and asthma
The researchers also investigated conditions that increased the likelihood of infants acquiring these beneficial bacteria.
"It is remarkable that children born vaginally were 14 times more likely to acquire the bifidobacteria from their mothers. In addition, exclusive breastfeeding and contact with other young children during early life also contributed to increased abundance of these bifidobacteria in the gut. This means that natural mechanisms help to prevent the development of these diseases. However, our lifestyle has contributed to these bifidobacteria becoming much rarer, and it is therefore also important to look at other preventive measures that can help infants who are not colonized with them," says Rasmus Kaae Dehli, specialist in systems immunology at DTU Bioengineering.
The results indicate that the addition of 4-OH-PLA or probiotic bacteria that can produce the substance may become a new strategy for preventing allergies and asthma. The researchers see potential in developing dietary supplements for those who are fully breastfed or infant formula enriched with these bifidobacteria or their metabolites. This could open for targeted efforts in the critical window of opportunity in the first months of life, when the immune system is formed.
Professor Susanne Brix Pedersen is a collaborator on the BEGIN study at Aarhus University Hospital, which concerns the early prevention of asthma and allergies, and where one of the bifidobacteria that the researchers have demonstrated a positive effect of is given to infants.
If the trials at Aarhus University Hospital show positive effects, Susanne Brix Pedersen estimates that a possible new preventive strategy for young children could be ready within a few years. For the treatment of patients with allergies or asthma, the timeline is longer, up to ten years, since a drug must first be formulated and then tested in clinical trials before it can be brought to the market.
DTU has taken out a patent on the use of the metabolite in medicines for the prevention and treatment of allergies and asthma.
