Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children

Abstract

BACKGROUND The Amish and Hutterites are U.S. agricultural populations whose lifestyles are remarkably similar in many respects but whose farming practices, in particular, are distinct; the former follow traditional farming practices whereas the latter use industrialized farming practices. The populations also show striking disparities in the prevalence of asthma, and little is known about the immune responses underlying these disparities. METHODS We studied environmental exposures, genetic ancestry, and immune profiles among 60 Amish and Hutterite children, measuring levels of allergens and endotoxins and assessing the microbiome composition of indoor dust samples. Whole blood was collected to measure serum IgE levels, cytokine responses, and gene expression, and peripheral-blood leukocytes were phenotyped with flow cytometry. The effects of dust extracts obtained from Amish and Hutterite homes on immune and airway responses were assessed in a murine model of experimental allergic asthma. RESULTS Despite the similar genetic ancestries and lifestyles of Amish and Hutterite children, the prevalence of asthma and allergic sensitization was 4 and 6 times as low in the Amish, whereas median endotoxin levels in Amish house dust was 6.8 times as high. Differences in microbial composition were also observed in dust samples from Amish and Hutterite homes. Profound differences in the proportions, phenotypes, and functions of innate immune cells were also found between the two groups of children. In a mouse model of experimental allergic asthma, the intranasal instillation of dust extracts from Amish but not Hutterite homes significantly inhibited airway hyperreactivity and eosinophilia. These protective effects were abrogated in mice that were deficient in MyD88 and Trif, molecules that are critical in innate immune signaling. CONCLUSIONS The results of our studies in humans and mice indicate that the Amish environment provides protection against asthma by engaging and shaping the innate immune response. (Funded by the National Institutes of Health and others.)

Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood

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“…Furthermore, they found an inverse correlation between the probability of developing asthma and the number of bacteria and fungi groups detected via 16S rRNA and traditional BARCELONA RESPIRATORY NETWORK culture techniques in dust collected from the respective household 75 . In order to further understand the effect of the impact of the environmental microbial contact on the development of asthma, Stein et al 76 studied two distinct, endogamous farming subgroups in the US, the Amish and Hutterites, two populations that are genetically more similar than other European populations. They have very similar lifestyles and risk factors for asthma, except the Amish use traditional farming methods, with frequent contact with farm animals, while the Hutterites live on highly mechanized communal farms.…”