High income countries are undergoing a massive increase in chronic inflammatory disorders, at least partly due to a failure of immunoregulation. A review in PNAS from Prof Graham Rook at UCLH explores how exposure to the “right” microorganisms (so called ‘old friends’) is crucial for the development of an effective immune system.
Early microbial exposures teach the body how to differentiate friend and foe, fundamentally affect the development of the crucial gut microbiome and prime the development of a functional immune system. Without these exposures, the immune system may attack self (leading to autoimmune diseases), attack harmless airborne particles (leading to allergic disorders such as hay fever), attack gut contents (leading to inflammatory bowel disease), or not be able to turn off background inflammation (leading to cardiovascular disease).
So, what are the most useful early microbial exposures to prime the immune system? The “hygiene hypothesis” suggests that we are ‘too clean for our own good’. However, Dr Rook suggests that exposures to a diverse group of our microbiological ‘old friends’ is what the immune system needs to develop properly, not indiscriminate microbial exposure, which will result in unnecessary exposure to harmful pathogens. Exposure to some of our ‘old friends’ (such as the worm-like parasitic helmiths) has been lost altogether in developed countries, and exposure to other microorganisms has been changed fundamentally by our urban living. Put another way, we should not allow our children to lick the toilet bowl, but should not discourage them from eating a bit of soil occasionally!
Where could this lead? Perhaps we could develop synthetic ‘crapsules’ to augment microbially deficient youngsters (in the same way that vitamin D supplements can be useful)? Or maybe the careful administration of our worm-like parasite old friends (helminths) would help to halt the progression or even reverse the course of previously incurable diseases (such as multiple sclerosis)?
I love the description of a newborn human as a computer loaded with programs (genetics) but no data, and that the type of data entered will affect how the computer functions. Also, the idea that our limited understanding of the depth, breadth and complexity of the microbial world based on the microbes we can grow in the lab can be likened to ‘microbial dark matter’. Notwithstanding the substantial gaps in our understanding, it seems that exposure to our microbial ‘old friends’ early in life is the best way to reverse the worrying trend in chronic inflammatory disorders for future generations.
Photo credit: Jay Reimer.
Reflections on Infection Prevention and Control 
Very interesting approach, even facinating. Too good to be true!!!!
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These new findings are definitely “good news for hygiene”, but my concern is how we change public perception about this misnamed hypothesis. Calling it the “hygiene” hypothesis fuelled the idea that we have become too clean for our own good, and still persists in the minds of the public, the media and others, despite the fact that most immunological experts agree the “Old Friends” hypothesis offers a more rational explanation, and is better supported by the epidemiological and other data.
In the 1950s our parents, armed with clean water, sanitation, vaccines, antibiotics and so on, were relieved that we could at last cut ourselves free of our pathogenic enemies. What none of us realised was that we had also been cutting ourselves off from our so called “Old Friends” which occupy the same habitats. The challenge we face is to reintroduce the microbes we need to our human bodies without reintroducing the disease- causing organisms. We need to dislodge the idea that children who have more infections are less likely to develop allergies. New data suggests that lifestyle changes which could be beneficial range from encouraging natural childbirth, sustained breastfeeding and physical interaction between siblings, to designing our homes to ensure more interaction with our environment, or encouraging more sport and other outdoor activities.
Because the terms ‘hygiene’ and ‘cleanliness’ are used inter¬changeably, to many people ‘being too clean’ implies the need to be less partic¬ular about hygiene which is a worrying trend. Several times recently I have heard mothers who say “I don’t bother to get my children to wash their hands anymore because I have heard they are more likely to get allergies”. As Graham Rook says “How do we persuade people that relaxing hygiene would not expose us to “Old Friends” – only to new enemies like E. coli O104”.
It seems likely, that, in the future, as happened in the 1950s, we will need to undergo another fundamental change in our thinking about our microbial world. We will have to persuade people to adopt a more balanced approach, where hygiene measures are targeted at breaking the chain of infection transmission when and where there is infection risk, rather than seeing hygiene as synonymous with home cleanliness.
If you are interested in learning more about this issue go to: http://www.ifh-homehygiene.org/best-practice-review/hygiene-hypothesis-and-its-implications-home-hygiene-lifestyle-and-public
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Thank-you Sally. I recommend that everybody reads the excellent summary that IFH have produced on this issue linked by Sally above.
The truth is that this is a subtle argument. For example, I suspect that children who have more illness in childhood probably ARE less likely to develop allergies later in life because exposure to the ‘old friends’ comes hand-in-hand with exposure to pathogens (feel free to correct me if I’m wrong here). As you say, as our understanding of the microbiology, immunology and epigeneitcs involved evolves, we need to find ways to promote exposure to our ‘old friends’ without exposure to the pathogens.
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