Our genes, or our environment?
A fascinating study focused on the Amish and Hutterite farming communities sheds light on how children develop allergies and asthma.
While the arrival of spring means much awaited warmer weather in many parts of the country, for many, it also means the arrival of allergens. Pollens from plant life and molds thriving from rainfall can trigger hay fever and asthma—very common conditions that if you don’t suffer from one yourself, you almost certainly know someone who does.
Asthma, allergies, and eczema tend to run in families, and there are quite clearly genetic factors that contribute to the risk of developing one or more of these conditions. But there are also factors in the living environment contribute to the risk of developing these conditions.
One such factor is exposure to farm animals; studies have shown that children exposed to farm animals—and the environmental bacteria that hang around with them—tend to develop asthma less often. But is it the exposure to farm animals that causes this, or is it just that families who farm simply have a lower risk for asthma to begin with?
Teasing apart what is genetic versus what is a product of the environment is really challenging, since genetically similar people—like extended families—frequently live in the same environment, eat the same foods, and are exposed to the same allergens. So if a child develops asthma, how could we know if it is a result of genetic risk factors, environmental risk factors, or both?
A natural experiment could really help here. If genetically similar people were exposed to different environments for reasons that were unrelated to their genetic risk for asthma, it would be possible to tease apart the influence of environmental factors from the genetic ones.
A 2016 study found one such natural experiment happening right here in the U.S.—in South Dakota and Indiana, to be more precise.
The Amish and The Hutterites
The Amish and the Hutterites are two groups of farming communities in the U.S. who, along with the Mennonites, share a common ethnic and religious background that traces back to the religious movements of 16th century Europe. The study authors—a large group of researchers with expertise in asthma, genetics, immunology, allergy, and environmental science—wrote in the New England Journal of Medicine:
We designed a study that compares two distinctive U.S. farming populations—the Amish of Indiana and the Hutterites of South Dakota… These two particular groups of farmers originated in Europe—the Amish in Switzerland and the Hutterites in South Tyrol [Northern Italy]—during the Protestant Reformation and then emigrated to the United States in the 1700s and 1800s, respectively.
Both groups have since remained reproductively isolated. Their lifestyles are similar with respect to most of the factors known to influence the risk of asthma, including large sibship size, high rates of childhood vaccination, diets rich in fat, salt, and raw milk, low rates of childhood obesity, long durations of breast-feeding, minimal exposure to tobacco smoke and air pollution, and taboos against indoor pets.
However, whereas the Amish practice traditional farming, live on single-family dairy farms, and use horses for fieldwork and transportation, the Hutterites live on large, highly industrialized, communal farms.
So the Amish and the Hutterites share common ancestry and have similar lifestyles when it comes to family life and diet. Where they differ is the amount of exposure they have to animals, since the Amish spend much more time face-to-face with animals while farming compared to the Hutterites, such as by plowing a field with horses (top photo of an Amish farm) rather than industrial machinery (a Hutterite farm below).
What does this have to do with asthma? The study authors continue:
Strikingly, the prevalence of asthma in Amish versus Hutterite schoolchildren is 5.2% versus 21.3% and the prevalence of allergic sensitization is 7.2% versus 33.3%, as previously reported.
Assuming the Amish and the Hutterites are indeed genetically similar after generations of “reproductive isolation” as the authors put it, they would be at a similar genetic risk of asthma. This would leave differences in non-genetic risk factors for asthma as the underlying cause of the differences in the asthma rates between Amish and Hutterite children.
The data
Researchers collected data on 30 Amish and 30 Hutterite children, matching them by age and sex to ensure they were similar groups to compare. They sampled the children’s blood to analyze their DNA and measure levels of immune reactivity. They then went into 10 Amish and 10 Hutterite homes, collecting dust in the air and vacuuming the floor and mattresses to measure the allergens present in each of the homes.
Their findings? First, they were able to confirm the assumption that after so many generations in the U.S., these children still shared common ancestry. Their genetic profiles were highly similar, suggesting the Amish and Hutterite children would have similar genetic risk for asthma.
Consistent with the previous research on asthma in Amish and Hutterite children, they found that none of the Amish children had asthma, while 6 (20%) of the Hutterite children did.
Amish children had lower levels of IgE—the antibody type most commonly associated with allergy and asthma—against common allergens than Hutterite children; meanwhile, levels of the non-allergic antibody types were similar. Amish children also had lower levels of eosinophils (the white blood cells implicated in severe allergic responses) and differing profiles of overall immune reactivity in their blood.
As far as allergen levels in the home, common allergens (from cats, dogs, dust mites, and cockroaches) were found in 4 out of 10 Amish homes but only 1 of 10 Hutterite homes. Levels of environmental bacteria in the air were 6.8 times higher in Amish compared to Hutterite homes, with differing profiles of bacterial species found in the mattresses.
Taken together, it appears that while as a group, Amish and Hutterite children share genetic risk factors, they live in significantly different environments when it comes to allergen exposure. Amish children are exposed to more animals, more allergens, and more environmental bacteria. Yet they have less asthma, and their blood samples show lower levels of allergy by several measures.
What gives?
The Hygiene Hypothesis
Simply put, the “hygiene hypothesis” reflects current scientific thinking that overly-clean environments can lead to the development of asthma and allergies—that regular exposure to aspects of our environment helps suppress immune responses that lead to allergy. If the immune system regularly encounters certain substances—such as fragments of environmental bacteria—it will be less likely to generate the types of immune responses that generate asthma or severe allergic reactions.
The hygiene hypothesis was sitting right there at the center of the Amish and Hutterite study: the Amish were encountering more animals, more dust, and more bacteria while developing less asthma than the Hutterites. This alone supports the hygiene hypothesis, but the researchers took it one step further.
It’s possible to artificially induce asthma in laboratory mice by exposing them to a chemical called ovalbumin, which tends to induce an allergic immune response. When the mice are exposed to ovalbumin again, they develop signs of asthma.
So the researchers took a group of laboratory mice and exposed them to ovalbumin in an attempt to induce asthma. But they also exposed the mice to extracts of the dust they collected from the Amish and Hutterite homes. They found that the mice who inhaled extracts of Amish house dust were protected against developing ovalbumin-induced asthma, while the mice who inhaled Hutterite house dust weren't and went on to develop asthma.
The bottom line
Because they share common ancestry and remain genetically similar, the Amish and Hutterite communities in the U.S. created a unique opportunity to understand how environmental factors influence the risk of developing allergic conditions like asthma. And even though their study was small with only 60 kids, this clever set of researchers made the most of the natural experiment sitting in front of them.
Simply observing that two genetically-similar groups—with similar diets and similar lifestyles other than their use of animals versus machinery—have different rates of asthma is enough to tell us that there must be something different in their environment contributing to the risk of asthma. These researchers took the initiative to then go out and measure what, exactly, that might be, making a pretty good case for exposure to animal and environmental bacteria.