Final Report Summary - HERA (Host-environment interactions in the protection from asthma and allergies) Asthma, allergic rhinitis and atopy are complex diseases in which genetic and environmental determinants play a role. Many genes with small effects act in concert with a multitude of environmental exposures to convey the asthma phenotype. It has been consistently shown in many studies around the world that children growing up on traditional farms are significantly protected from developing asthma and allergies. This protection is mostly mediated by exposure to animal shed and the consumption of unprocessed cow’s milk early in life. Animal sheds are rich in microbial exposures such as bacteria, archaea and fungi. Work within the HERA project using novel DNA based sequencing methods and advanced statistical analyses has shown that the diversity of both, bacterial and fungal environmental exposures protects from the development of childhood asthma. These findings clearly suggest that there is not one protective factor but many. In fact protection is most likely accounted by a cocktail of Gram positive and negative bacteria and fungi from the environment. This diverse environmental exposure is likely to influence the human microbiome which is more abundant in and on us than human cells. Each body habitat harbors a characteristic microbiome and recent studies revealed the existence of a lower airway microbiome. The microbiome in asthmatic airways has an altered bacterial composition as compared to the microbiome in healthy airways. An increased abundance of the phylum Proteobacteria to which Moraxella catarrhalis, Haemophilus influenza and Streptococcus pneumonia belong was seen in asthmatic samples. There is furthermore evidence that gut microbial colonization does not only have a local but also a systemic immune regulatory effect and may therefore impact on the development of asthma and allergies. The HERA project has investigated the association between the environmental and the human microbiome and their relative role in the protection from asthma and allergies. Beside the microbiome, immune-stimulating substances derived from environmental bacteria and fungi such as endotoxin and extracellular polysaccharides are also likely to contribute to the allergy protective effect seen in traditional farming environments. In turn, the role of genetic factors seems less pronounced. In a recent gene*environment analysis very little effect of genetic factors was seen.
