Here's a look at the latest science on what leads to a healthy immune system.
Whether we’re aware of it or not, many of us are living with immune systems that are slightly out of whack—and, incidentally, making us feel miserable. Take allergies, for example. If you’re an allergy sufferer, you have a lot of company. Maybe it’s pollen that makes your nose twitch, or maybe you—or your child—have a nut allergy that threatens to send you to the emergency room if you accidentally eat something that contains the slightest trace of peanuts. An allergy is the product of an overactive immune system—the body’s natural defenses against infection mobilized against harmless foreign particles.
Asthma is another form of allergic disease, and has its own serious consequences. Like allergies, it often develops in childhood and can be treated, but not cured. And then there are autoimmune diseases—less common but often more debilitating than allergic diseases—including conditions such as lupus and multiple sclerosis. These diseases are caused when the immune system starts attacking the body itself.
Both allergic and autoimmune diseases are on the rise in the United States, and researchers have been working to understand why. In fact, there’s a pretty solid theory about what’s going on. It’s called the “hygiene hypothesis,” and it helps explain a curious fact that has been documented by recent research: You’re less likely to develop allergies and asthma if you grow up on a farm.
I started my research by calling Mark Holbreich, an allergist who has worked in Indiana since 1987. Both he and his wife are physicians, and several years ago, they began to treat people within the local Amish community, many of whom did not have easy access to medical care. But Holbreich quickly realized there was relatively little need for his services among the Amish. They had surprisingly low rates of allergy—even many of the people who came to him for treatment turned out to have other conditions, not allergic diseases.
As it turned out, a similar phenomenon had already been documented in Europe. “Around 2002, the first literature appeared in a German study that coined the term ‘the farm effect,’” Holbreich says. The researchers were looking at asthma and allergy rates among farming families, and found that those who worked in barns around large livestock were less likely to have these conditions. “When that article came out, I said, ‘Gee, that sounds like the Amish.’ And in 2010, I began a collaboration with German researchers,” Holbreich says. The resulting article was published in 2012 in the Journal of Allergy and Clinical Immunology.
The European study subjects lived in rural parts of Switzerland, and the Amish community in Indiana was living a similar agrarian lifestyle. “We decided to do a study looking at how common allergies were in these children,” Holbreich says. “We weren’t looking necessarily for illness, but for a positive skin test, what we call allergic sensitization.” If you test children in the general population for allergies, about 50 percent will have at least one positive skin test. “In the Swiss farm children, it was about 25 percent; in the Amish children, it was about 7 percent,” Holbreich says. That’s a huge difference—so now the question was, why?
To Holbreich and the other researchers, three protective factors stood out: “First, when the mothers are pregnant they spend time around large animals like cows,” he says. “Second, the children are in the barn at a very early age; and third, the children drink raw, unpasteurized milk.”
Before we go any further, Holbreich wants to be clear that he doesn’t recommend drinking raw milk. “For children and pregnant women, raw milk presents a large risk,” he says. Drinking unpasteurized milk could potentially expose people to dangerous pathogens.
It also seems unlikely that you could get the same effect just by the occasional visit to a farm. After all, the studies in Switzerland were comparing farm kids not to urban dwellers but to other rural children. “I think it’s the whole picture: living on a farm, being pregnant on a farm,” Holbreich says.
In fact, there aren’t many actions we can take right this minute based on research on the farm effect. But it does give us a better idea of how our immune systems work—or why they might not be working—and points us toward therapies that might solve those problems.
This research also helps illuminate the theory about immunity called the hygiene hypothesis. For more information on that area of research, Holbreich recommended I talk to Dr. Andy Liu at National Jewish Health, a Denver hospital and research center that specializes in respiratory diseases. He also mentioned a book that was recently published on this topic, An Epidemic of Absence, by Moises Valasquez-Manoff, which focuses not just on allergic conditions, but also autoimmune diseases.
When I called Liu to talk about the farm effect studies, he explained that these ideas are not as new as we might think. “People have been thinking about it almost since allergy was discovered 150 or so years ago,” he says. “You can see when people are writing about it they’re asking, ‘Why is it happening to these people who are living in cities and with educated backgrounds, and not happening to farmers or not happening to the poor?’”
It may seem counterintuitive that wealthier people would be the ones getting sicker, but that’s exactly the trend with allergies and asthma. It’s happened in many other countries, Liu explains: As average incomes rise, so do the rates of asthma and allergies.
“Some people think the roots of it are in public or personal hygiene. That’s where the term hygiene hypothesis comes from,” Liu says. This line of thinking suggests that improved sanitation around the early 1900s meant that people encountered fewer germs. While on the whole, improvements such as cleaner drinking water had major benefits for public health, there may also have been some unintended effects. It seems that early exposure to various microbes may actually help us develop healthy immune systems that stay with us for the rest of our lives. “With the hygiene hypothesis, it’s about the immune system and its period of learning,” Liu says.
Specifically, the hygiene hypothesis considers how the immune system learns to regulate itself, how it learns when to launch a full-scale assault against infection and when to calm down because those defenses aren’t needed. “Without the development of that appropriate regulation you see the immune system going after things that it shouldn’t necessarily go after,” Liu says. For example, with hay fever, the symptoms are caused by an overactive immune system attacking pollen as though it were an infectious agent.
The idea that our immune systems seem to have a critical period of learning shouldn’t be surprising, Liu says, because we see it in other areas of development. “It happens with the brain, too—with infants. When they don’t receive stimulation, they fail to thrive.”
How exactly this works is still unfolding, but exposures early in life, including in the womb, seem to be important. There’s also some question of whether it’s simply that we are exposed to microbes that matters, or if there are specific protective microbes. Or both. In any case, farms are a great place to study this. “The farms are rich in microbial environments,” Liu says. “A lot of it seems to be related to animals or to the other people we’re around. To the extent that we can quantify microbial burdens, it’s much higher in farm homes.” You also find richer microbial environments in homes with pets or many young children.
Some of the broader implications of the hygiene hypothesis relate to all kinds of immune dysfunction—not only allergies and asthma, but also autoimmune diseases. But so far, most of the research focuses on allergies and asthma because they are more widespread. “Autoimmunity is so much less prevalent that it’s hard to do population studies,” Liu says. “If you think of the most common autoimmune conditions, you need maybe a hundred times more people to show the same effect compared to allergies.”
On the more extreme end of the spectrum, researchers are experimenting with some really interesting treatments related to the hygiene hypothesis. It’s not just microbes that researchers are examining, but also parasites. That may sound far out, but Liu points me to a clinical study in which a type of pig whipworm is being tested as a treatment for Crohn’s disease, an autoimmune disorder. But more about parasites in a minute.
Finally, I spoke to Moises Valasquez-Manoff, author of An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases. The title points to the underlying idea: It’s not so much what we’re exposed to that’s causing these diseases, it’s the conditions we evolved with that are now missing. As a result, “The immune system is missing critical input, or at least that’s what the theories sort of predict,” Valasquez-Manoff says.
He’s done an immense amount of research for the book, and I wanted to ask something that had been nagging me: Why are we sure it’s not cleaner farm air that’s leading to lower rates of asthma and allergies? Surely these conditions are tied to air pollution? Well, for quite a few reasons, he explains.
“One way to think about the pollution question is simply to look at the epidemiology. At least in terms of airborne pollution, if you were to graph asthma and pollution, the graphs are inverse of each other,” he says. After the Clean Air Act in the 1970s, air pollution in the United States started to decline. At the same time, asthma rates were shooting up. Studies have also been done in East and West Germany. Before the wall fell, East Germany was much more polluted, but it also had lower rates of asthma and allergies than West Germany. “Now, each new generation is more allergic than the previous one in the East.”
Plus, there were the original farm effect studies in Switzerland. “Those studies were in pristine areas of the Alps, where there was no pollution.” Regardless, the researchers found that farm kids had much lower rates of allergy and asthma compared with their rural neighbors, all of whom were breathing exceptionally clean air.
That’s not to say that air pollution doesn’t have an effect on allergies and asthma. “I think we should unwed ourselves from the idea that there’s only one cause for everything,” Valasquez-Manoff says. “And I’m not going to say that breathing car exhaust every day is good for you. But in terms of the greater trend, I think there’s something else going on that’s more biological.”
With the farm effect studies, the low rates of allergies and asthma for farm-raised people appears to point to exposure to microbes, whereas the increase in allergic and autoimmune disease for Americans relates to lack of exposure. Most of us simply aren’t in daily contact with the kinds of microbes our ancestors lived with for thousands of years. People who live on small farms often are. “You think about this in an evolutionary context and you realize that the sort of environment we evolved in much more resembles a Bavarian cowshed than it does a modern apartment in New York or San Francisco,” Valasquez-Manoff says.
And while we’re on the topic, there’s something else that’s missing from many of our lives: parasites. It’s probably not just microbes teaching our immune systems how to regulate themselves. Quite a bit of evidence points out that parasites do the same thing—and have done so for the thousands of years that our ancestors lived with many kinds of worms. Valasquez-Manoff, in fact, infected himself with hookworms as a part of the research for his book because it’s an underground treatment for some autoimmune conditions.
Of course, no one recommends hookworm infection as an allergy treatment. And in research on the farm effect, all the evidence points more strongly toward beneficial microbes (which, fortunately, means that any therapies that come out of that research are likely to be a lot less disturbing).
“Maybe it is just really going to be a probiotic,” Valasquez-Manoff says. Or maybe it will be as simple as drinking milk. Researchers are looking closely at raw milk, and what it is that seems to be offering protection against allergies and asthma. “Whatever it is, we all drink milk, and if you can just preserve it in regular milk, it’s a very easy intervention,” Valasquez-Manoff says. What if we found a new technique for sanitizing milk that improves upon pasteurization? We might be able to destroy the pathogens while preserving whatever it is that’s beneficial. Or the solution could be as simple as adding beneficial compounds to milk in the same way we add vitamin D. “Can you imagine?” Valasquez-Manoff asks. “It would be incredible.”
■ In 2001, one out of 14 people in the United States had asthma. By 2009, it had increased to one in 12.
■ Between 4 and 6 percent of children in the United States have food allergies. This rate increased by 18 percent between 1997 and 2007.
■ 90 percent of food allergy reactions come from the following eight types of food: cow’s milk, eggs, peanuts, tree nuts, fish, shellfish, soybeans and wheat.
■ 18 million adults in the United States (about 8 percent of the population) have hay fever; 7 million children (9.5 percent) have hay fever.
Megan E. Phelps is a freelance writer living in Lawrence, Kansas. After researching this article, she likes cows more than ever, but is not so sure about tapeworms.
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