Friday, 13 April 2012

Let them eat mud

The hygiene hypothesis has always appealed to me. I like dirt. I like playing in dirt. I’ll believe just about anything that gives me a good reason to do something that feels a bit naughty. I love the concept of “good fat”. I’m sure ice cream is full of it (although I make a point of never checking).

The hygiene hypothesis states that children need exposure to infectious agents early in life to ensure the normal development of their immune systems, and that without this exposure they will become atopic. Atopy refers to the inappropriate activation of the immune system that can cause allergies, eczema, and asthma. The hygiene hypothesis was originally proposed to explain why children from larger families have fewer allergies. The theory is that children from large families are exposed to more infectious agents through their siblings, and these good and necessary immune stimulations prevent the bad and unneccesary immune stimulations later in life known as allergies. It’s as though the immune system gets bored if it has nothing to do and starts attacking anything it can get its dirty little hands on. Get a few more colds as a kid and you won’t have allergies. Let your kids play in the dirt. Sounds like a good idea. Given my partner’s family history of allergies and my daughter’s infantile eczema and milk sensitivities, I particularly liked the idea of pro-actively preventing future allergies in my children. I’ve never actually looked into the science of it, and it’s about time.

The immune system is fascinating and dynamic. It is comprised of T cells, B cells, macrophages and a few others. The B cells produce antibodies. The macrophages eat things like parasites, bacteria and viruses. The T cells just help. They recognize the infection and can either help the macrophages (in what’s known as a Th1 response) or the B cells (Th2 response). Allergies are all Th2 since they involve the production of IgE from B cells, which then causes histamine release from mast cells (mast cells fall into my broad category of “other” immune cells).

Evidence for the hygiene hypothesis comes from 2 sources: epidemiology and mouse experiments. There are a number of interesting mouse models of atopic diseases. A few weeks ago, a paper in Science argued that mice raised in a germ-free environment were more prone to allergic asthma. Exposure to germs as a newborn could reverse this, while exposure during adulthood did little. The mouse evidence is quite nice, and definitely supports the hygiene hypothesis.

Epidemiology doesn’t establish causes, but it’s about the only way to find correlations in human populations. Epidemiology showed us the correlation between smoking and lung cancer. It can produce powerful information. The epidemiological data supporting the hygiene hypothesis are as follows:

1. Children from large families are less likely to have hay fever and eczema
2. Allergies and asthma have been increasing dramatically in developed countries in recent decades, where hygiene standards have also been improving

There are a couple of glaring issues with the epidemiological data. Asthma can have a variety of underlying pathologies and is more like a bunch of different diseases which all look the same. Some types of asthma are immune-related, some are not. It’s about a 50:50 split. Changes in the incidence of asthma are therefore inaccurate indicators of atopy. Furthermore, the incidence of asthma in the developed world is now on the decline (with the notable exception of inner-city African Americans). Despite the popularity of the hygiene hypothesis, I don’t think we’re any dirtier than we were 10 years ago. Given the number of handbag-sized hand sanitizers on offer at my local drugstore, it might be the opposite. A recent world-wide WHO study showed a U-shaped relationship between GDP and asthma, further undermining the hygiene hypothesis as an explanation for increasing asthma in developed countries. The poorest and the richest countries tend to have more asthma and wheezing than those in the middle. Even if we take asthma out of the picture altogether, the evidence for increasing atopy of any kind in the developed world is unclear. Some countries are experiencing declines, others are not. The epidemiological evidence for the hygiene hypothesis is sketchy at best, even though the hypothesis originated there.

In its original form the hygiene hypothesis argued that Th1 responses early in life (the macrophage-stimulating ones) could prevent subsequent inappropriate Th2 responses (the antibody-producing ones). But there’s a bit of an adaptation of that original hypothesis that seems to hold more weight. It’s not as much about exposure to infectious agents as it is about repeated, low-dose exposure to the allergens themselves. It’s more about inducing tolerance than it is about immune-skewing. Epidemiology can help here, too. Farming and early exposure to pets are associated with lower incidences of allergies and asthma, and that data is relatively robust. Recent allergy-prevention strategies involve low-dose shots of allergen in an attempt to induce immune tolerance. They don’t cause disease and they don’t induce immune responses.

Perhaps the hygiene hypothesis should be renamed. I’m not convinced that my kids need to come into contact with every infectious agent that causes the outpouring of fluids from noses, mouths and bums, but I’m glad to see that there is some evidence that letting them play in the mud and pet strange dogs might help them avoid future allergies. And if current allergy-prevention strategies are a good indicator, perhaps low-dose exposures even as an adult can induce tolerance. Yay for dirt.

1 comment:

  1. I had asthma when i was in Edinburgh. Then it disappeared after a year in london. Now I'm in Bristol and the tickly cough seems to be turning up again.
    My theory is that traveling on the tube actually gave my immune system something to do and that's why the cough left. Now i'm in a relatively "cleaner" environment I think my immune system is getting bored...