Advertisers fetishise germ-free kitchens and bathrooms where the threat of “harmful bacteria” is always lurking but can be eradicated with mop or a wipe.
Meanwhile, the media is full of alarming reports about the growing number of people with auto-immune and allergic diseases – the figure has more than doubled in the past 20 years.
One of the theories seeking to explain this exclusively Western epidemic is called the hygiene hypothesis: too much cleanliness is responsible for the immune abnormalities that cause auto-immune and allergic diseases.
But before we start embracing dirt, let’s stop and consider what we actually know about why so many people are getting these diseases and what needs to be done to change this.
The hygiene hypothesis
The hygiene hypothesis was developed in the United Kingdom to explain the rise in the number of people suffering from hay fever, which had been quite rare at the beginning of the 19th century.
Curiously, in the 1980s, UK children were found to be less likely to develop hay fever if they had older siblings. Younger siblings did not have the same protective effect.
The original publication about this by David Strachan concluded that “allergic diseases were prevented by infection in early childhood, transmitted by unhygienic contact with older siblings, or acquired prenatally from a mother infected by contact with her older children."
“Over the past century,” Strachan continued, “declining family size, improvements in household amenities, and higher standards of personal cleanliness have reduced the opportunity for cross infection in young families.”
The hygiene hypothesis rapidly gained support as an explanation for rising rates of allergic diseases. It explained why these diseases continued to rise despite – or indeed, because of – improvements in public health measures.
More recently, excessive hygiene has also been blamed for the rise in auto-immune diseases, including type 1 diabetes and multiple sclerosis. Inflammatory diseases such as Crohn’s disease and ulcerative colitis are also on the rise.
There appears to be plenty of evidence in support of the hypothesis: the steady increase in disease incidence with rising – and therefore more hygienic – living standards in Western countries; the sharp increase of disease rates in children born to migrant families after their arrival in Western countries; and the protective effect of factors such as early childcare, which tends to reduce hygiene.
So, how does “hygiene” predispose people to immune-mediated disease? The short answer is that we don’t actually know.
While the migration studies, the rising incidence and the effect of birth order suggest an infectious cause, no one has pinpointed the responsible micro organism.
Suggestions include any number of common childhood infections, certain types of microbes and parasites prevalent in “dirt” or passed on by pets and farm animals, and even normal micro organisms present within our gut or on our skin.
Many studies have tested for correlations between lifestyle factors, such as living on a farm, and the incidence of immune-mediated disease.
But, as always with correlations, it is difficult to be sure which environmental/hygiene factors are responsible.
We know the infections involved aren’t the ones we vaccinate against, since vaccinations do not differentially affect siblings. And they didn’t produce a corresponding spike in immune-mediated diseases when they were introduced.
An alternative approach to understanding immune-mediated disease
One way of narrowing down the possible environmental/hygiene factors that cause immune-related disease is to approach the problem from the other end – by seeking to understand the immune system itself, and how environmental/hygiene factors could impact on its function.
For this approach, the discovery of a small but absolutely essential subset of T cells within the immune system has been vital. Regulatory T cells or Tregs (pronounced tee-regs) are unique in their ability to control unwanted immune responses, such as allergies and autoimmune diseases.
Children with non-functional Tregs die during infancy or childhood due to an over-active of the immune system. These deaths are caused by severe allergies and an aggressive autoimmune attack on many organs.
Tregs – the intelligence officers of the immune system
So how do Tregs work? Our own research at Sydney’s Centenary Institute has indicated that Tregs set the threshold for immune activation.
This means they allow the immune system to concentrate on dealing with serious infections by turning off responses to low-level microbial threats.
Tregs are the intelligence officers of the immune system, constantly interpreting the signals from the frontline where potentially harmful microbes are first encountered.
We propose that Tregs need to process a wide range of microbial information in order to appropriately set the immune threshold. When the threshold is at the right level, potentially threatening infections are perceived to be above the threshold and generate a rapid immune response.
Harmless environmental substances, on the other hand, fall below the threshold and are therefore ignored.
When Tregs are deprived of microbial information sources, they can set the threshold too low. Then the immune system mistakenly reacts to totally harmless substances. These include allergens, leading to allergic diseases such as hayfever, and the body’s own organs, leading to autoimmune diseases such as type 1 diabetes.
Since Tregs modulate the immune threshold in real time, even temporary disturbances in Treg function have the potential to cause detrimental allergic or autoimmune responses.
Like other immune cells, Tregs are distributed throughout the body, particularly at the sites where we are likely to encounter disease-causing microbes.
The most important site is the gastrointestinal tract (the GIT) where up to 90% of our immune cells are located.
An inside-out focus for the immune system
Somewhat paradoxically, your GIT, which is inside you, has by far the biggest area of interaction with the outside world – approximately 300 square metres compared to two square metres of skin.
It is also populated by a massive number of microbes: Your GIT contains between 10 and 100 trillion foreign organisms that are essential to your health.
The microbes that live within our guts are the obvious candidate for the source of harmless microbes to keep Tregs functioning normally.
Not only do they make up by far the majority of microbes that the immune system encounters on a daily basis, but they are established in early infancy and maintained throughout life in an essentially stable symbiotic relationship.
This dovetails neatly with the hygiene hypothesis because it explains how an infectious event early in life (colonisation of the gut with bowel flora) can produce a life-long effect on the immune system.
We are only just starting to understand our gut microbes, many of which cannot be cultured and were discovered only by sequencing their DNA.
There is now a massive sequencing effort – the Human Microbiome Project – which, like the Human Genome Project, will serve as the foundation of further studies to understand our gut microbes.
Hygiene and the GIT
So, how does hygiene affect gut bacteria? First, we need to think about where the bacteria come from. The first and most important source is from our mothers during the birth process.
Babies born under very hygienic conditions, particularly by caesarian section, show a significant delay in colonisation by gut bacteria, and acquire significantly fewer different organisms.
Thus, they start life with a relatively impoverished gut microbial ecosystem.
There is already evidence that the metabolic products of gut bacteria can have crucial effects on development of allergic disease in infants.
A recent report has also indicated effects on cardiovascular disease. These reports come from developed countries that may already have lost significant components of a healthy gut microbial ecosystem due to generations of hygienic practices.
The question that is most pressing at the moment is: Will we be in time to preserve “natural” human gut ecosystems before the entire human population is irreversibly affected by “hygiene”?