Do environmental factors alter the human genome?
Thanks to precise genetic analysis, scientists can identify risk genes that make the onset of a certain disease more likely. More and more research is also being done on the interplay between genes and the environment, which determines whether a genetic risk constellation develops into a disease. One example of this is a Europe-wide study that examines the development of allergies and asthma in children from farming families and compares them with their peers who did not grow up on farms.
In asthmatics, certain gene segments in the genome, so-called alleles, are found that 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 in school than children who do not carry the risk allele.
As part of the Europe-wide PASTURE study, children from birth to adolescence who grew up in a farm environment were regularly examined for the development of allergies and asthma and compared with their peers who did not grow up on farms. The international study team had already shown in previous studies that children who lived on farms rarely suffered from allergic diseases or bronchial asthma. These studies showed that close contact with stable animals, their proximity to living and sleeping areas as well as the regular consumption of non-processed 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 was also effective in children who, as carriers of a risk allele for asthma, were particularly susceptible to the chronic lung disease. They therefore only examined children who had the corresponding allele to see whether they developed persistent wheezing in early childhood and/or bronchial asthma in school-age children. 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 were wheezing or developed asthma than in those who did not develop the disease despite their genetic disposition. 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 disposition.
Effect of fresh, non-processed 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 farm factors that mediates the protection of genetically predisposed children. The corresponding analysis of the study data showed that children who drank non-processed, fresh cow's milk daily developed an active immune response and were less likely to develop asthma than children who did not drink this "farm milk". The researchers concluded from their results that this protection must be mediated via the oral route and the gut flora. "We were able to support this result with analyses of the children's stool samples," says Dr. Sabina Illi from the Institute for Asthma and Allergy Prevention at Helmholtz Zentrum München. "These showed that special intestinal bacteria had accumulated in the children drinking farm milk, which produce immune-stimulating metabolic products." According to the researchers' hypothesis, immune cells activated by these bacteria travel via the lymphatic system from the intestine to the lungs, where they can prevent inflammatory processes in the bronchial tubes.
"Future studies should show whether the allergy-protective effect emanating from 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 is where new preventive treatment methods could come in.“
Quality-assured biobanking of study samples
In biomedical long-term studies, scientists rely on the quality-assured processing and storage of biosamples, because only the professional and standardised handling of the sample material guarantees a valid and comparable determination of measured variables even after longer storage periods. "We are pleased," 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 taking care of the study samples in a quality-assured manner, which is important for the determination of immunological markers.“
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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
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