Does getting dirty make a kid healthier? Yes, if he or she is a laboratory mouse

If you're like me, you think that it's healthy for kids to play in the dirt and wrestle with dogs and suffer through a cold now and then. I think of it as giving your immune system a workout. That way, when it runs into something like the H1N1 flu virus, it's got some muscles built up--in the form of lots of B and T cells and antibodies. That's the hope.

The immune system's more complicated than that, but the basic theory that it's good for kids to eat dirt is known as the "hygiene hypothesis." The subtlety, according to the theory,  is that a lack of exposure to microbes prevents the immune system from developing a tolerance for certain antigens, and leaves the body more likely to develop auto-immune diseases. Last week the hygiene hypothesis got some support in the form of laboratory experiments conducted on mice by a team of researchers in Boston and Kiel, Germany.

In their paper, published in Science [nice news story in Nature too], the scientists explain how they worked with two types of mice--one, "germ-free," devoid of any bacteria or protozoa or viruses (except viruses already integrated into their DNA), and the other, "specific-pathogen-free," which they don't describe very well but which you assume have well-established symbiotic gut microbes but aren't infected with any diseases. The germ-free mice, the authors find, have increased numbers (compared to the SPF mice) of white blood cells called "invariant natural killer T cells," which can detect certain kinds of molecules associated with infection; cause inflammation when they're activated; and have been linked to both inflammatory bowel disease (IBD) and asthma.

The germ-free mice had increased numbers of NKT cells in just their colons and lungs, and were far more susceptible than the SPF mice to laboratory models of asthma and IBD.

But when the scientists exposed pregnant germ-free mother mice to the same living conditions as the SPF mice, so that they and their newborns could acquire a population of gut microbes, the thus-exposed "germ-free" baby mice went on to develop relatively normal populations of NKT cells, and were protected from getting asthma and IBD.

However, allowing adult germ-free mice to build their own gut flora did not protect those mice from asthma and IBD. So it seems there's a window in which young mice must be exposed to microbes--to play in the dirt, as it were--if they are to get any benefit.

Because this paper was published in Science--about as high-profile as it gets--I'm guessing that clear evidence supporting the hygiene hypothesis is sparse. What conclusion could you draw from this research?

No human child, excepting the Bubble Boy, is brought up in an environment remotely resembling that in which germ-free mice are maintained. We're all crawling with bugs inside and out; dirty whether we like it or not. But Western society is quite keen on taking antibiotics to treat bacterial infection. And most antibiotics are pretty indiscriminate in what they kill. That's why the pharmacist warns you that your digestion may be upset while you pop Amoxicillin. It clears out your intestines.

So giving very young children oral antibiotics unnecessarily could be doing them harm in the long run by depriving them of gut microbes during a critical window--and those kids could grow up more likely to develop asthma and IBD.

Does the hygiene hypothesis, and this research in particular, apply to eczema? I put this question to Jon Hanifin, MD, a dermatologist at Oregon Health Sciences University, and am hoping to hear back from him.

[Monday, March 26] And here are his replies:

Question 1 : is this research relevant to atopic dermatitis? (are natural killer cells involved in AD?)

JH: It would be pretty speculative to claim relevance to AD but the "hygiene hypothesis" has been suggested for all the atopic conditions for many years and maybe this model will provide some some basis for testing the hypothesis. NK cells have probably been studied in AD just like all the others but much of the work with any of the T cells can be misleading so it is best to step back and look at the larger picture.

Question 2: if so, is there anything usable for patients, extrapolating from the results; could it possibly be that infants in modern society/urban centers aren't being exposed early on to the "right" mix of/number of nonpathogenic microbes?

JH: Not much at this point--presumably infants get exposed to all the microbes parents carry.  The idea that farm kids get a broader palette seemed to have some validity for respiratory allergies but not much for AD. The greater AD incidence in urban kids might reflect more barrier damage from use of irritating/drying skin care products.

Eczema and the hygiene hypothesis

There's a story making the media rounds right now, based on an article in press at the Journal of Allergy and Clinical Immunology. In a nutshell: if women work on farms, or live with cats, while they are pregnant, the children they then give birth to are about 20% less likely to develop eczema. The results came out of a population study conducted by an international, mostly European group. Readable Reuters version of the story here.

One result is particularly interesting-- the finding that the children's risk of developing eczema dropped further with each additional species of animal to which the mothers were exposed. For three or more animals, the risk of eczema dropped to 50% compared to the average population. This "dose-response" is convincing evidence that the effect is real.

This supports the "hygiene hypothesis," that increasing numbers of people in the developed world are getting allergic disorders because they're not exposed enough to microbes when they're young. The hygiene hypothesis says that if you're exposed to bacteria etc. from pigs, cows, and sheep, the type 1 helper T cell arm of your immune system gets a good workout, and this suppresses the overactive type 2 helper T cell arm found in allergic disorders.

But: so what? This kind of research is neat, but you wonder what we are supposed to do with it. Not everyone has, or wants, the opportunity to muck out horse stalls so that their offspring have their chances of getting eczema reduced by 20%.

And cats--what's up with that? There's a lot of research out there showing that cat dander is a major allergen for eczema. Perhaps you should keep a cat until the moment of birth, and then give it away and vacuum the house thoroughly.

The study's authors (as one would expect of academics) make the caveat that "we did not study infectious diseases." So these kids who didn't develop eczema may have developed all kinds of other problems caused by microbes from animals.

This suggests that we need not abandon the hypothesis of good hygiene. I'm the dad of two kids under 4, and I know all too well where they put their hands. They need to be washed.