Is there clear evidence for the hygiene hypothesis?

The problem lies in the misleading term "Hygiene Hypothesis". It is certain that our immune systems are malfunctioning because of diminished microbial exposures and diminished "microbial data input", but it is increasingly clear that hygiene does not play a major role in causing this diminished exposure.  Much more important causes of the problem are outlined below.

What we see in modern, particularly urban, communities is an increase in disorders where the immune system’s control mechanisms are failing so that it attacks things it should ignore. For example, in autoimmune diseases like multiple sclerosis our immune systems are attacking our own tissues. Similarly our immune systems attack harmless molecules in the air, or in food (allergies) or they attack the contents of our guts which contributes to inflammatory bowel diseases. But in addition to attacking these “forbidden targets” we also find that the immune system is causing persistent systemic background inflammation in an increasing percentage of the population. Inflammatory responses should only occur when they are needed as part of our defence and repair mechanisms. Then when the job is done, inflammation should switch off completely, but in the modern world it often stays active. This is serious because persistent background inflammation is associated with disorders of the heart and metabolism, neurodegenerative disease and psychiatric disorders. To describe these manifestations of inappropriate over-activity of the immune system as “weakening” is clearly silly.  

So what is happening? The vertebrate immune system has co-evolved, over about 500 million years, with an increasingly complex gut microbiota (the community of mostly symbiotic organisms that live in and on us, particularly in our guts). The microbiota plays an essential role in driving the development and function of essentially all our organs (including the brain), but particularly the development of the immune system, and of the mechanisms that regulate it.

 Similarly our airways need exposure in early life, to microbial components from the natural environment that provide signals involved in setting up the appropriate background level of activity of the immune system, and above all, appropriate activity of anti-inflammatory regulatory mechanisms in those sites. We know that the natural environment plays a crucial role thanks to numerous studies of different types of home and of farming communities.

The natural environment also plays a crucial role in supplying the spores of human-gut-adapted bacterial strains, so that these can be “re-installed” when needed. Obviously wherever humans have lived, the environment has been seeded with these spores, which persist for many centuries.

Finally, if we encounter a very wide range of microorganisms in early life the immune system develops a larger repertoire of memory lymphocytes. This increases the chance of there being some that recognise novel pathogens that we might meet in the future. Only in this limited sense does diminishing microbial exposure lead to any “weakening”.

In summary, the vertebrate immune system is a learning system like the brain, and without various microbial inputs that provide essential data it cannot function correctly. But what aspects of modern life lead to loss of the necessary microbial contacts? 

First (in a chronological sense) caesarean deliveries and some inappropriate hygiene might inhibit transfer of maternal microbiota to the infant. I emphasise that all other hygiene, particularly hand-washing, is entirely beneficial, and people who try to persuade the public that hygiene is bad are as foolish and dangerous and the anti-vaccine lobby that is killing increasing numbers of children by removing protection from measles.

The second most important factor is the overuse of antibiotics, particularly during pregnancy and in early life. Repeated courses of antibiotics increase the incidence of allergies, other inflammatory disorders, and obesity.

The third factor is the bad Western diet. The biodiversity of the gut microbiota is maintained by a varied diet, and by fibre (plant cell walls) and plant polyphenols that nourish crucial beneficial microbial species, several of which help to drive the immunoregulatory pathways.

A fourth factor is lack of exposure to the natural environment. Keeping a dog in the home partially compensates, because the dog brings the environment into the home. But walking and exercising in green spaces, and gardening are the best solutions.

In conclusion, I am not aware of any data that confirm claims that home hygiene is “weakening the immune system”…. (whatever that may mean).  Major lifestyle changes (diet, antibiotics, lack of exposure to the natural environment) are leading to defective education of our immune systems, and to disorders attributable to failing immunoregulation. We clearly need to rename the hygiene hypothesis. Recent suggestions include"Biodiversity hypothesis" and "Old Friends Hypothesis".