Environmental Mechanisms of Asthma Protection: Studies on Amish and Hutterite Farm Dust

Abstract

Introduction: Asthma is a chronic inflammatory disease of the airways. It is the most common chronic disease of childhood and the leading cause of hospitalization among children. Asthma is a complex disease with genetic, developmental, and environmental factors contributing to the disease pathogenicity. The rapid increase in asthma rates in the last several decades has led us to focus on the environmental component in asthma. Children who grow up on small traditional family farms are protected against asthma and allergies. The asthma rates among the European farmers and non-farmers are recapitulated in two US based populations, Indiana Amish and South Dakota Hutterites. The two populations share similar farming lifestyles, have large families, have similar diets, and share a common ancestry. These two communities part in the way in which they farm. The Amish practice traditional, small single family farming, while the Hutterites use state of the art technology in their highly mechanized farms that are located at the edges of their colonies. Amish are strongly protected against asthma, while Hutterites have rates that are comparable to the ones in the general population. We hypothesized that environmental exposures impact innate immune responses leading to decreased asthma risk. Methods: We utilized murine models of experimental asthma to determine the effects of aqueous extracts prepared from barn and house dust samples collected from Amish and Hutterite farms. Results: Amish house dust extract reduced OVA-induced airway hyperresponsiveness, airway inflammation and serum IgE, while Hutterite house dust extract did not. Administration of Amish dust extract to mice lacking MyD88 and TRIF, adaptors for TLR signaling, resulted in the abrogation of the protective effect seen in wild type animals. Investigation of the effects of Hutterite barn dust extract revealed that this extract was able to reduce house dust mite induced airway hyperresponsiveness and airway inflammation to a degree comparable to Amish barn extract. Furthermore, a time-course analysis showed that the effects of the extracts became apparent after twelve days and include increases in airway inflammatory markers. Flow cytometry analysis of total lung cells revealed an increase in CD3+RORγt+γδcells that was accompanied by an increase in IL17 expression. Lastly, transfer of gut microbiota from a healthy Amish child to germ free mice led to a time-dependent decrease in airway hyperresponsiveness and IL13 expression in the lungs. Conclusions: We have demonstrated that Amish and Hutterite environmental products are sufficient to recapitulate profiles of asthma susceptibility seen among Amish and Hutterite children, therefore demonstrating that the environment plays an important role in asthma susceptibility in this communities. Innate immunity plays an essential role in mediating the protective effects of Amish dust extracts. Amish fecal microbiota might influence asthma rates among the Amish.