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Mice Dig Holes in the “Hygiene Hypothesis”

New evidence suggests exposure to microbes in early childhood might not protect against allergies.

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An empire of dirt awaits the newborn baby: dirty floors, dirty yards, dirty pets, dirty toys. In recent years, many parents have taken to letting their babies roam this scuzzy terrain freely without immediately applying soap and scrub brush. The dirtier, the better.

The parents are motivated by the “hygiene hypothesis,” a popular theory that posits that excessive cleanliness can reduce germs needed to educate the immune systems of babies and young kids. This, according to the hypothesis, could put children at higher risk for certain kinds of ailments, like asthma and allergic diseases, later in life. 

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Having fewer siblings meant fewer colds and flus in one’s very early life.

Many attribute the hygiene hypothesis to a 1989 paper by David Strachan, a British epidemiologist who studied chronic disease, and particularly allergies and respiratory ailments, such as asthma, which were rising meteorically then as they are today. (Asthma is now the most common chronic disease in the world.) 

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Over the past decade or so, the hypothesis has become a darling of immunologists and has been widely covered by the media. But in the process, Strachan’s original ideas were oversimplified, he has pointed out—it was never just about exposure to a diversity of bacteria in one’s early years but also to specific infections during critical time windows after birth. In any case, good data showing a direct link between clean environments and allergies has been frustratingly scarce, Strachan has noted—at least in part because long-term epidemiological studies in humans are so difficult to complete. 

Now, a new study with mice—some clean and others dirty—is further complicating this narrative. 

For their study, a team of scientists in Sweden selected two types of mice. The “clean” cohort were fairly typical lab mice, which live in conditions that aren’t that different from most modern humans: They dwell in relatively clean cages, don’t carry diseases common in their wild relatives, and eat food that is mostly free of germs. 

Gathering the “dirty” cohort took a little more work. The researchers didn’t want to just use mice from the wild, because they might look genetically different from the lab mice, which could influence the results. So the researchers implanted lab mouse embryos into surrogate mothers from the wild, generating what they dubbed “wildling” mice. When the baby wildling mice were born, the researchers housed them in environments more typical of the wild—layered with hay, compost, and other natural materials containing microorganisms normally found in nature. As they grew, the wildling pups from different litters were allowed to socialize with each other to increase their microbial exposures.

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The dirty upbringing of the wildling mice did not prevent them from developing allergies.

In the end, the wildling mice developed gut, skin, and vaginal microbiota that were more like those of their “dirty” wild brethren than those of their clean lab cousins. “The young mice, they’re born to mothers that are also ‘dirty,’ and so they’re exposed to microbes and get antibodies from day one, or even in utero,” says Susanne Nylén, associate professor in the department of microbiology, tumor, and cell biology at the Karolinska Institutet, who was one of the authors of the study, which was published in Science Immunology.

And yet, the scientists were shocked to find that the dirty upbringing of the wildling mice did not lessen their chances of developing allergies. In fact, the wildling mice developed immune responses to allergens that were more powerful than those of the clean lab mice—higher T-cell counts and antibodies, more inflammation and mucus, all of which are consistent with what happens when people with allergies are exposed to certain infectious agents. 

“It was a little bit surprising or maybe it made our life a bit more difficult” to note the strength of this response, says Jonathan Coquet, associate professor in the same department at the Karolinska Institutet, and also a study author.

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Do their findings disprove the hygiene hypothesis? Not exactly. For one thing, mouse pups are different from human kids. Still, the results suggest that exposing babies to dirt and microbes isn’t a panacea, says Nylén. “There’s no quick fix like that.” The causes of allergic responses are more nuanced and complex: Our genes, the food we eat, the polluted air we breathe, the toxins we absorb from the environment in the form of pesticides or forever chemicals all play a role in predisposing some of us.

But yes, let children play in the sandbox and tussle with their filthy pets. Playing in the dirt is still a very healthy part of being a kid.

Lead image: Regreto / Shutterstock

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