Asthmatics have certain gene segments in their genome, known as alleles, which contribute to the risk of developing asthma. Children who carry this allele develop very typical persistent breathing noises - wheezing - as early as infancy. They are significantly more likely to develop asthma at school age than children who are not carriers of the risk allele.
As part of the Europe-wide PASTURE study, children who grew up in a traditional farm environment were regularly examined from birth to adolescence for the development of allergies and asthma and compared with their peers who did not grow up in a farming family. The international study team had already been able to show in previous studies that children who lived on traditional farms rarely suffered from allergic diseases or bronchial asthma. These studies showed that close contact with barn animals, their proximity to the living and sleeping areas and the regular consumption of unprocessed cow's milk protected farm children from allergic-inflammatory diseases.
Protected despite genetic predisposition
The study team now wanted to know whether the protection against asthma also applies to children who, as carriers of a risk allele for asthma, are particularly susceptible to the chronic lung disease. They therefore only examined children who had the corresponding allele to see whether they developed persistent wheezing and/or bronchial asthma during early childhood. The study showed that the number of asthmatics in the group of farm children was indeed significantly lower than in the non-farm comparison group. A deeper look into the children's immune system also showed that the immune response to microbial germs was significantly weaker in the children who had gout or developed asthma than in those who did not develop the disease despite having a genetic predisposition. The scientists attributed this result to the strong immune stimulation provided by a diverse farm microflora, which is also able to protect children with a genetic predisposition.
Effect of fresh, unprocessed cow's milk
Next, the study team asked whether the effect observed here could be attributed to a specific farm factor or whether it is the sum of the farm factors that mediates the protection of genetically predisposed children. The corresponding analysis of the study data showed that children who drank unprocessed, fresh cow's milk every day developed an active immune response and were less likely to develop asthma than children who did not enjoy this "farm milk". The researchers concluded from their results that this protection must be mediated via the oral route and the intestinal flora. "We were able to support this result by analysing stool samples from the children," says Dr Sabina Illi from the Institute for Asthma and Allergy Prevention at Helmholtz Munich - German Research Center for Environmental Health. "These showed that special intestinal bacteria that produce immunostimulatory metabolites had accumulated in the children drinking farm milk." According to the researchers' hypothesis, immune cells activated in this way travel via the lymphatic system from the intestine to the lungs, where they can prevent inflammatory processes in the bronchi.
"Future studies should show whether the allergy-protective effect of farm milk directly shuts down the risk alleles or whether other mechanisms mediate this effect," explains Prof Dr Erika von Mutius, Head of the Munich Institute for Asthma and Allergy Prevention. "This could be the starting point for new preventive treatment methods."
Quality-assured biobanking of study samples
In long-term biomedical studies, scientists are dependent on the quality-assured processing and storage of biosamples, as only the professional and standardised storage of samples guarantees the valid and comparable determination of measured variables, even after long storage periods. "We are delighted," says Prof. Dr Dr Petra Ina Pfefferle from the Comprehensive BioBank Marburg (CBBMR), "that we were able to contribute to the success of the study and that my team is providing quality-assured care for the study samples, which are important for the determination of immunological markers."
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Scientific publication
Illi S et al, Immune Responsiveness to LPS Determines Risk of Childhood Wheeze and Asthma in 17q21 Risk Allele Carriers. Am J Respir Crit Care Med (2022) DOI: 10.1164/rccm.202106-1458OC
