Examining the Hygiene Hypothesis and the Role of the Microbiome in Allergic Disease

The relationship between the microbial environment and the development of allergic diseases has been under scrutiny for a long time. Speaking on February 21, 2015, at the American Academy of Allergy, Asthma and Immunology’s 2015 annual conference in Houston, TX, Erika Von Mutius, MD, MSc, discussed the origins of the hygiene hypothesis and the role of the microbiome in allergic diseases. Von Mutius is head of the Asthma and Allergy Department of the Dr. von Hauner Children’s Hospital of the University of Munich, Germany.

In 1989, Strachan described for the first time an inverse association between the number of siblings and the incidence of hay fever. The higher the number of siblings, the lower the incidence of the disease. He hypothesized that infections early in life decrease the incidence of atopic allergic diseases. In 1994, Mutius was able to obtain similar results when she evaluated data from patients from East and West Germany. Since then numerous epidemiological studies have confirmed this inverse association.

In order to understand the mechanisms behind this association, Mutius has evaluated data from a large cross-sectional study conducted in Germany. She has observed that children from farm houses that used coal heating had lower incidence of asthma, airway responsiveness, wheezing, and hay fever, and lower levels of IgE when compared to infants who lived in houses without coal heating. These results suggested that exposure to a rural environment could prevent the development of allergic diseases. Indeed, data from a study in Switzerland has confirmed that Amish children raised in farms had lower incidence of hay fever and wheezing and used less steroid medication when compared to children who lived in urban areas. Mutius believes that the increased number of siblings and exposure to stables in farms have a protective effect against allergic diseases, although the mechanisms behind these two factors seem to be different.

Asthma is one of the most important allergic diseases and, according to Mutius, there are three different clinical presentations: transient wheezers, non-atopic wheezers and IgE-associated wheezers. To differentiate which type of asthma is affected by exposure to farming environment, Mutius and collaborators evaluated 8000 children age 6-12 years. They concluded that exposure to a farming environment had a positive effect on atopic sensitization, lung function, transient wheezing, and wheezing associated with viral infections.

To investigate if early exposure to farming environment interferes with allergic diseases, they also conducted a large birth cohort study (the PASTURE study) with 1,100 pregnant women who lived in farms or not. They concluded that maternal farming exposure had important effects on the newborn and during the first year of life, increasing the expression of regulatory T-cells, TNF-alpha, and interferon gamma, and decreasing the incidence of atopic dermatitis. The early exposure of children to a farming environment has also been shown to decrease the incidence of wheezing, rhinitis, and infectious rhinitis. It is believed that this early exposure decreases the incidence of asthma.

Currently, researchers are trying to identify the source of this protective effect and are studying the microbial DNA present in dust from stables. So far, numerous bacteria and fungi have been identified, and it has been observed that the higher the number of bacteria and fungi in the dust, the lower the incidence of asthma in children. However, it is not clear yet how these microbes affect human health. According to Mutius, the microbiome present in the nose has important correlation with the development of asthma—the greater the microbiome diversity in the nose, the lower the incidence of asthma in children. The same, however, is not valid for the lower airways.

In summary, farming exposure seems to have an overall protective effect on the development of allergic diseases. The more diverse the microbiome is, the greater the protective effect. The precise role of the microbiome in health and disease, however, remains to be solved.