A recent study led by Dr. Alex Mira (FISABIO, Spain) and Dr. Maria C. Jenmalm (Linköping University, Sweden) and researchers at IATA-CSIC (Spain) has presented an analysis of a total of 192 faecal samples from 28 healthy children and 20 children developing allergic symptoms at age seven, from when the children were 1 and 12 months of age. It has found that children who develop asthma or allergies later in life have altered immune responses to intestinal bacteria in the gut mucosal environment at an early age. The results also suggest that the mother’s immune system may play a role in the development of asthma and allergies in children.
Majda Dzidic, first author of the study, corresponded with GMFH editors about the significance of the work.
What is already known and what have you already found about the role of gut microbiota in allergic diseases? Why do the first 2-3 years of life appear to represent the most critical period for microbiota modulation to reduce children’s risk of asthma and allergic disease?
We believe that the first years of life are crucial when it comes to the maturation of a healthy gut. This early period of childhood is also known as a “critical window of opportunity” [when] the infant’s immune system is being instructed on how to react against (and tolerate) the symbiotic microbiota. Mucous membranes are present in the airways and gastrointestinal tract and here they come into contact with large amounts of bacteria and viruses. IgA antibodies, [principal] primary [mediators] of humoral mucosal immunity, are present in mucous membranes. Here they bind to microorganisms that they recognize and act as a barrier, preventing them from entering the mucosal tissue and creating immune responses that might damage the surrounding tissue. [Besides] the fact that the microbial recognition by maternal and infant IgA antibodies must be appropriately orchestrated for an optimal maturation of the mucosal immune system, the microbiota itself plays a central role in this early immune modulation. So we believe that diversity and composition [of] the bacteria are major drivers for the normal maturation of a healthy mucous membrane. Thus, perturbations in this symbiotic relationship between the immune system and intestinal microbiota, during the early period of life, seem to be highly correlated with the child’s risk of asthma and allergic disease development.
What are the most relevant new findings in your research group regarding the effects of gut microbiota on asthma and allergy development during the first years of life? What does your newest study add?
This is the first study where the role of mucosal immune responses towards the gut microbiota, in relation to childhood allergy development, has been addressed. By investigating the bacterial taxa that were targeted or not by IgA antibodies, we could confirm the importance of early life intestinal microbiota for later allergy development. We saw that the children who subsequently developed allergies had a lower fraction of IgA antibodies bound to their intestinal bacteria at one year of age compared to those children who stayed healthy. This was particularly manifested in children who developed asthma during the first seven years of life. We could also detect the differences in the types of bacteria that were targeted by the immune system of these two groups of children, as early [as] one month of age. These interesting results are suggesting that the barrier function of the mucous membranes is less effective in children who develop allergies later in life and that this can be monitored already during the first year after birth.
What is the role of the mother’s immune system and breastfeeding in childhood allergy development?
Studies and clinical reports suggest that secretory IgA that [originates] from the mother’s breast milk is important for immune regulation and protection against many infections in suckling infants. In this study we were interested to note that the differences in intestinal microbiota IgA responses were obvious in infants as young as one month. This was surprising since the IgA antibodies in children that young come largely from the mother, through breast milk. Moreover, all the infants included in the study were exclusively breastfed until at least one month of age. So it seems that the immune response of the mother and the antibodies that the child receives in breast milk are connected with the development of allergies. This is something we want to look at in more detail in future work.
Based on your study, what kind of potential interventions do you suggest to combat the current asthma and allergy epidemic?
We are still far from understanding what is defining a healthy gut microbiome that promotes tolerance and prevents allergy development. I would say that the interventions enhancing infant mucosal barrier function, such as prebiotic/probiotic supplementation and [encouraging] exclusive breastfeeding during the first months of life (6 months according the WHO guidelines), may represent efficacious preventive strategies required to combat the asthma and allergy epidemic. Also, we should work on reducing the use of antibiotics and encourage children to play outside, thus increasing the microbial exposure important for healthy immune system development.
What further steps are you planning to take in the way of using gut microbiota as a biomarker for identifying infants with increased risk of asthma and allergic disease?
We think that the early characterization of IgA coating patterns of intestinal microbiota may represent a possible way to identify infants with increased risk to develop asthma and allergic disease later in life. Although this needs to be confirmed in larger cohorts, it paves the way to develop diagnostic kits to identify children with high risk so preventive strategies, including those aiming to enhance gut diversity, can be directed towards that population group. Also, it would be of great interest to detect what factors in breast milk, reflecting the immune response of the mother, are connected with the development of allergies. This is something we are planning to investigate in more detail.
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