Farm Living Study Confirms the Hygiene Hypothesis

Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children

Stein MM, Hrusch CL, Gozdz J, et al
N Engl J Med. 2016;375:411-421

Background

The hygiene hypothesis of atopy was first introduced in 1989,^[1] but there has not been a uniform definition of the term. The surge in atopic disease has been ascribed to reduced childhood viral infections owing to vaccination, increased antibiotic use, reduced helminth exposure, and urban living.^[2]

Although some of these theories are debatable,^[3] the inverse correlation between farm animal exposure and atopy has been one of the more intriguing observations. However, the mechanism of and the degree of exposure necessary for this protection had not been established.

The Study

Stein and colleagues compared the Amish community of Indiana with the Hutterites of South Dakota. These two insular farming communities are strikingly similar genetically and environmentally, except that the Amish practice "traditional farming" on single-family farms, whereas the Hutterites' farms are highly industrialized. Past studies have noted that the respective rates of atopy and asthma are much higher in the Hutterites (33% and 21%, respectively)^[4] than the Amish (7% and 5%).^[5]

The study looked at asthma prevalence and the clinical and immunologic characteristics of atopic disease of children in both groups, and assessed the human and mouse model responses to house dust. None of the 30 Amish children had asthma, but six of the 30 Hutterite children did (20%). The Amish children had much lower total and allergen-specific levels of immunoglobulin (Ig) E and eosinophil counts, despite having similar exposure to allergens. Amish children had higher neutrophil counts and lived in homes with much more endotoxin (levels nearly seven times higher) than those of the Hutterites. A pooled dust sample identified differences in bacterial profiles as well.

To investigate the suspicion that the house dust was in itself the immune-modifying agent, the investigators compared the effects of Amish vs Hutterite house dust in a classic ovalbumin mouse model of allergic asthma. Hutterite dust was not protective against ovalbumin-induced allergic inflammation. Amish dust extracts, however, were able to significantly inhibit ovalbumin-induced airway hyperresponsiveness, bronchoalveolar lavage eosinophilia, and serum ovalbumin-specific IgE.

The results clearly show that something in Amish house dust is capable of preventing allergic sensitization, probably owing to endotoxin or other microbial products. Those in turn act on the innate immune system. The study found differences in proportions and gene-expression profiles of peripheral blood immune cells and in the genes involved in innate immune responses to microbes. The amount and phenotypes of neutrophils, eosinophils, and monocytes were also different. Genes associated with innate immune pathways seem to have been turned on by the microbes in the Amish environment.

Viewpoint

These are exciting times in the field of allergy and asthma. Expensive biologicals offer hope for patients with severe asthma, but who will pay for them? Primary prevention of atopy and asthma is the best way to contain costs, and now it appears that there may a way—but only if the innate immune-stimulating elements of the microbes can be isolated.

Abstract