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A mechanism for hygiene hypothesis

by Ari LeVaux

My son’s first taste of solid “food” was dirt licked from a freshly dug parsnip. He’s hardly the only kid to grow up with a dirty spoon in his mouth, but it’s understandable that parents want to prevent such culinary adventures. Many illnesses are caused by exposure to microorganisms, which tend to hang out in dirty places. But a growing body of epidemiological studies suggests that early exposure to microbes is crucial to the development of a healthy immune system.

Correlations are strong between early-life exposure to microbes and lifelong absence of asthma, allergies, eczema and other autoimmune diseases. The relationship, dubbed the hygiene hypothesis, has been repeatedly confirmed in the last two decades, but there remains scant information as to how it might actually work. Now, research published March 22 in Science proposes a mechanism for the hygiene hypothesis. If this research can be extended to humans, it could lead the medical community to modify its use of antibiotics and provide parents a whole new perspective on mud pie.

The paper, titled “Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function,” is the first study to make headway in explaining a mechanism, perhaps one of many, behind the hygiene hypothesis – at least in mice. A research team led by Dr. Richard Blumberg and Dr. Dennis Kasper of Brigham and Women’s Hospital in Boston studied “germ-free” mice that were born and raised in a sterile environment and treated with antibiotics. Compared to mice that were allowed normal contact with microbes, the germ-free mice had exaggerated inflammation of their lungs and colon reminiscent of what you’d associate with asthma and colitis. The team attributed the inflammations to increased levels of specialized white blood cells called invariant natural killer T (iNKT) cells, which they detected in the lungs and bowels of the germ-free mice. The iNKT cells, and resulting inflammation of lungs and bowels, did not go away when the mice were exposed to microbes later in life.

One model for the hygiene hypothesis speculates that insufficient exposure to pathogens stunted parts of the immune system, causing other parts to become too powerful and overcompensate, leading to autoimmune disorders like allergies and asthma. The recent work of Blumberg et al appears to validate this explanation, filling in some of the blanks. The iNKT cells called to action in germ-free mice could be real-life analogs to aspects of the overcompensating part of the human immune system.

While pleased with his team’s discovery, Dr. Blumberg told me by phone that before he can truly call the observed behavior of iNKT cells a mechanism, rather than a “potential mechanism,” two major hurdles need to be crossed.

“Now that we have a potential mechanism, we’re going to try to understand the specific microbes involved. The next step would be to show the same mechanism at work in humans.”

In addition to making parents rethink their fear of dirt, this research could bring about changes in which antibiotics are prescribed to kids and pregnant moms.

“If you’re going to look for an epidemiological correlation to what we’ve observed, it’s that early-life exposure to antibiotics might force a reduction in that protective colonization,” Blumberg told me. “But that’s speculation.”

In addition to antibiotic use, society’s war on germs involves antibacterial soaps and disinfectants, the pasteurization of milk, and maintenance of hyper-clean living environments. Of the 3 million different genes identifiable in our bodies, only 30,000 are human genes. Most of the rest are bacterial genes. By indiscriminately attacking the microbes in our lives, we may be attacking important parts of ourselves.

So should parents refuse antibiotics for their kids to ensure they don’t acquire autoimmune disorders? Blumberg isn’t going that far. “These are probabilities we’re talking about. Just because a person gets antibiotics early in life doesn’t mean it will necessarily be detrimental.”

A similar trade-off may be rising to the surface in the ongoing debate over unpasteurized milk. Raw milk has caused a slew of food-borne illness events, most recently Campylobacter outbreaks in California and Pennsylvania, which together sickened almost 100 people in recent months. On the other hand, drinking raw milk correlates with a reduced likelihood of asthma. An August 2011 paper in The Journal of Allergy and Clinical Immunology reported that children who drink raw milk have a 41percent lower risk of developing asthma and are about half as likely to develop hay fever, compared to kids who drink only store-bought pasteurized milk.

Blumberg declined to comment on the raw milk debate, other than stating generally, “... the benefits of our modern hygienic practices and use of antibiotics far outweigh the risks.” Until we better understand what’s behind the hygiene hypothesis, he advised, it’s best to continue washing our hands and taking our medicine.

If iNKT cell behavior like what the team reported can be found in humans, it would still provide only a piece of the puzzle. Many autoimmune diseases might have a genetic component as well. A child whose parents both have allergies has a 75 percent chance of developing allergies as well.

So is there a take-home message for expecting parents or those with young children? You won’t hear many people going on the record dissuading anyone from using antibiotics, vaccines, pasteurized milk, etc., despite their growing associations with autoimmune diseases. Because if getting too cozy with microbes doesn’t make you stronger, it could kill you.

Still, significant thought, and research dollars, are being put into the possibility that probiotics (beneficial, living bacteria in pill form) early in life could provide protection against autoimmune diseases. It’s no wonder that Blumberg wants to find out which ones are doing the heavy lifting in holding back the crush of iNKT cells in mice.

At the very least, it seems like yet another reason for pregnant moms and young families to get a plot at a community garden. Playing in the dirt and with other dirty children seems like a better idea than ever. How well you clean the parsnips is your call.