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Feb 16th: Cleaning up the hygiene hypothesis - is it time to throw out the hygiene hypothesis?”

This new feature article by Megan Scudellari  in this weeks edition of  Proceedings of the National Academy of Sciencesis a well-researched, thought provoking view on the rise of allergy and autoimmune diseases and shows how,  if looked at objectively, it’s obviously due to  “much more than rampant cleanliness”.  She also reflects on whether it is possible to abandon the term hygiene hypothesis and thereby detach the concept from its association with “hygiene” as the public understands it.

Megan traces the issue from the original “hygiene hypothesis,” proposal – the idea that the surge in autoimmune and allergic disorders and simultaneous sharp decline in mumps, measles, tuberculosis, and other infectious diseases in developed countries were connected in some way. Looked at more closely, however, the hypothesis immediately began to show cracks. Measles and many respiratory diseases proved not to be protective against allergic disease, and may even increase the risk.  The proposed biological mechanism also failed to hold up

In 2003, Graham Rook proposed a revised explanation, the “old friends” mechanism. This suggests that early and regular exposure to “old friends” microorganisms present throughout human evolution and recognized by the human immune system—train the immune system to react appropriately to threats. Rook likens the immune system to a computer: It has software, but it needs data—in the form of exposure to a diverse set of microbes—to train it to identify threats appropriately. It’s not about just learning what to attack, but learning what to tolerate. The problem comes when our immune system meets an allergen like pollen or peanuts and doesn’t know that is harmless.

Rook argues that hygiene in its broadest sense - radical improvements in sanitation, food, and water in the late 20th century were involved in reducing our exposure to microbes but  simultaneous changes in other factors most likely had an even larger influence especially in early life. Caesarean sections have been linked to increased risk of allergy and asthma; owning a pet or growing up on a farm is protective against them; and antibiotic use (which kills off both good and bad microbes) has been linked to asthma, cow’s milk allergy, IBD, and eczema. All of these have been altered simultaneously and overwhelmed the host’s ability to modulate the immune system.

Still, the catchy hygiene hypothesis is widely embraced by the public, the media, and even scientists. Meghan reports “Use of the term in the scientific literature rose threefold over the past 10 years compared with the decade prior, according to a search on Thomson Reuters Web of Science.

Scudellari goes to some lengths to understand the problems of “Cleaning up the hygiene hypothesis”. As she says, the trouble is that, as soon as you use the words ‘hygiene hypothesis,’ the word hygiene prejudges what the cause is. To the public, “hygiene” is interpreted as personal cleanliness: washing hands, keeping food clean and fresh, sanitizing the home. The term fails to incorporate the other factors now linked to increases in immunoregulatory diseases, like antibiotic use and diet.   Her interviews suggest however that the call to abandon the original simplistic theory is falling on deaf ears when it comes to scientific experts, who may have little interest in the impact on public attitudes to hygiene and its importance. Several researchers interviewed for the article said the issue was semantics, and they didn’t care what name is used. The main concern seems to be that they themselves as scientists understand that it now means the “Old Friends mechanism”. There appears to be little concern that when they use this term with less well informed consumer journalists, the journalists find it imperative to explain what  “hygiene hypothesis” means to their readers – namely the 1989 version of the hypothesis and the link to infection and hygiene.

In concluding her article Meghan looks to the future and concludes that although there are many studies supporting a theory that moves beyond the hygiene hypothesis, there are very few credible studies testing interventions to reregulate the immune system. She quotes Wills-Karp as saying “Researchers hope that, at some point, they will be able to identify which regulatory pathways train the immune system. If we could find common pathways, we could adopt drugs or probiotics to activate [those pathways] to condition the immune system properly in early life,” Any intervention will need to be done by 3 or 4 years of age, by which time a child’s microbiome is established and the immune system has completed much of its training. From an immunological standpoint, any therapeutic intervention also needs to be specific rather than dampeing the immune system in a nonspecific way,” Citing steroids as a case in point. Instead, individuals could be treated with a personalized microbial mixture that induces immune regulatory cells. “It’s a big challenge,” “but we need to start thinking about it.”

This may all seem exiting - but meanwhile the media will continue to persuade us that we have become too clean for our own good - and we need to stop washing our hands – despite the fact that this is probably the most cost effective means to reduce the global burden of infectious disease - and  key to tackling the global problem of antibiotic resistance?

The article is open access at http://www.pnas.org/content/114/7/1433.full.pdf