Is There Clear Evidence for the Hygiene Hypothesis?

Check out this answer from Consensus:

While there is substantial evidence supporting the hygiene hypothesis, particularly in relation to asthma, allergies, and autoimmune diseases, the strength of this evidence varies across different factors and conditions. Methodological limitations and the complexity of immune system interactions with the microbial environment necessitate further research. Future studies should aim to address these limitations and explore the hypothesis’s applicability to a wider range of diseases.

The hygiene hypothesis posits that a lack of early childhood exposure to infectious agents, symbiotic microorganisms, and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system. This hypothesis has been extended to explain the rise in autoimmune diseases and other inflammatory conditions in industrialized societies. This article reviews the current evidence supporting the hygiene hypothesis, drawing from multiple research studies to provide a comprehensive overview.

Historical Context and Evolution of the Hygiene Hypothesis

The hygiene hypothesis was initially formulated to explain the increasing prevalence of allergies in Western societies. It suggested that reduced exposure to infections and microorganisms in early life could lead to an increased risk of developing allergic diseases6. Over time, the hypothesis has been expanded to include autoimmune conditions and other inflammatory diseases, reflecting a broader understanding of the immune system’s interaction with the microbial environment2 3.

Key Factors and Evidence

Inflammatory Bowel Disease (IBD)

Research has explored the role of hygiene-related factors in the development of IBD. Factors such as H. pylori exposure, helminths, breastfeeding, and sibship have been identified as potentially significant, although the evidence varies in strength. Methodological shortcomings, particularly the reliance on retrospective data, complicate the assessment of these factors1.

Asthma and Allergies

The hygiene hypothesis has been extensively studied in the context of asthma and allergies. Epidemiological studies have shown that children raised in rural environments or on farms, where they are exposed to a diverse range of microorganisms, have lower rates of asthma and allergies compared to those raised in urban settings3 5. This “farm effect” is partly attributed to the immunomodulatory properties of endotoxins and other microbial products3.

Autoimmune Diseases

The hypothesis has also been extended to autoimmune diseases, suggesting that reduced microbial exposure may impair the immune system’s ability to distinguish between self and non-self, leading to autoimmune reactions. This is supported by evidence showing higher rates of autoimmune diseases in more hygienic, industrialized societies2 10.

Gender Differences

Gender differences in the prevalence of asthma, allergies, and autoimmune diseases have been linked to the hygiene hypothesis. Higher standards of cleanliness for girls compared to boys, especially in early childhood, may contribute to these differences. This gendered pattern of hygiene and its impact on immune health highlights the need for a nuanced understanding of the hypothesis7.

Mechanisms and Molecular Insights

Recent research has delved into the molecular mechanisms underlying the hygiene hypothesis. Toll-like receptor ligands and other bacterial products play a crucial role in modulating the immune system, particularly during early life. Genetic variations also influence the immune system’s response to environmental stimuli, suggesting a complex interplay between genetics and microbial exposure6.

Expanding the Scope

The hygiene hypothesis has shown adaptability in the face of new scientific developments. It now encompasses a broader range of diseases, including psychiatric disorders and cancer, and incorporates insights from epigenetic studies. This ongoing evolution underscores the hypothesis’s potential to provide a generalized explanation for health burdens in industrialized societies9.

 

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Is there clear evidence for the hygiene hypothesis?

Robert B. Clark, M.D has answered Near Certain

An expert from UConn Health in Immunology

There is clear evidence for the hygiene hypothesis. 

For example, studies have demonstrated increased asthma in genetically similar populations in which one population farms in an old fashioned and “dirtier” environment while the other population uses modern and “cleaner” farming methods. The cleaner population had a significantly increased frequency of asthma, suggesting that exposure to bacterial products in the dirtier environment “educates” and “acclimates” and essentially calms the immune system to environmental and self-stimuli, – so there is less of an over-reponse to both environmental and self stimuli (and less asthma). In the “cleaner” and more asthmatic environment, direct evidence was documented showing that the immune system over-reacts to such stimuli.  (Stein, M.M., et. al., 2016. N Engl J Med 375: 411-421. “Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children”).

The mechanism underlying this concept was also clearly modeled in a mouse model (Schuijs,M.J. et.al., 2015. Science 349:1106-1110. “Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells)).

 

Is there clear evidence for the hygiene hypothesis?

Cosby Stone has answered Likely

An expert from Vanderbilt University Medical Center in Immunology, Allergology

The central tenet of the hygiene hypothesis is that we have gone a bit too far and inadvertently killed off our good bacteria along with the bad. As our society progressed from one that was chronically burdened with infectious diseases caused by poor sanitation, the thinking goes, we reduced our exposures to the things that gave our immune system an appropriate training and tolerance. Historically, our totally rational fear of dying from a cholera epidemic led to sewage and water management, but may have kicked off the allergy epidemic.

Our overuse of antibiotics and C-sections affects the set of organisms called the microbiome that an infant is exposed to growing up. Both have been shown to increase the risk of childhood allergic diseases.

Growing up in a rural area exposed to farm animals appears to confer a decreased risk of allergies and asthma for your entire lifetime, even among genetically similar populations. Studies in mice have shown that inhaling certain molecules from soil-dwelling bacteria can set off a beneficial cascade promoting an immune system which focuses more on threats rather than nonthreats, such as allergens.

Vaccinations appear to be a crucial exception to the rule of the hygiene hypothesis. They confer protection against diseases without any associated increase in the risk of allergic disease, likely because they, unlike antibiotics, are very specifically targeting only the worst disease-causing organisms.

I have adapted this answer from my article that you can read in The Conversation.

 

Is there clear evidence for the hygiene hypothesis?

Marie-Claire Arrieta has answered Likely

An expert from University of Calgary in Microbiology, Immunology, Gastroenterology, Asthma

The Hygiene Hypothesis was born from work made by Dr. David Strachan, who observed that younger siblings were less susceptible to eczema and asthma, and proposed that this was a result of increased transmission of infectious agents via unhygienic practices within a household. This initial hypothesis was then reframed to incorporate the old friends/microbiota hypothesis, restricting exposures to defined commensal microorganisms (instead of solely pathogens) as the source of immunomodulatory signals preventive of the so-called “Western diseases”. These include immune a metabolic diseases such as asthma, allergies, obesity, diabetes, autoimmune disease, etc.

Evidence to date does support the notion of microbial encounters early in life as necessary for our immune system to develop, but there is no evidence (that I am aware) that links infectious diseases early on with a lower risk of immune-mediated diseases later in life. In this regard, the original concept of the Hygiene Hypothesis is not accurate. On the other hard, non-infectious microbial exposures are associated with lower risk of diseases, and alterations to these exposures (via antibiotics, for example) can lead to increased risk of diseases like asthma and obesity.

In terms of hygiene or cleanliness, there is evidence that children born and raised in farms have less risk of asthma than urban children, which does show that more microbe encounters (of the non-disease kind) may be advantageous. As long as risk of infectious disease is kept in check (by following proper hygiene measures) growing up in a less clean environment is likely beneficial. However, these benefits may be less important that proper infant nutrition (breastmilk), natural birth and less overuse of antibiotics.

 

Is there clear evidence for the hygiene hypothesis?

Graham A W Rook has answered Likely

An expert from University College London in Immunology

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”.

 

Is there clear evidence for the hygiene hypothesis?

Sharyn Clough has answered Likely

An expert from Oregon State University in Biology, Medicine

Epidemiological research across cultures seems to indicate that increased societal standards of hygiene and increasingly robust improvements to sanitation infrastructure (e.g., water cleanliness) are helpful for protecting people from a variety of diseases (as we’d expect) but have also resulted in unintended negative health consequences, especially with respect to immune health.

What is less clear is how to respond, which is usually what people want to know. With respect to my own work on the potential relationship between gendered differences in relevant disease rates (asthma, allergies, Lupus, arthritis, MS, Graves Disease, etc.) and differences in gender socialization in the global north and west with respect to higher standards of cleanliness for children identified as girls vs children identified as boys, I have often been asked whether we should encourage girls to eat dirt or at least play in it more often. There are two problems to think about when formulating a response.

The first is that the hygiene hypothesis is supported by large trends at the level of populations, and it is not always obvious whether and how these population trends affect any given individual.

Second, the idea that we can somehow distinguish between “good” germs/bacteria/parasites and “bad” is misconceived. These are complex organisms that are sometimes hard to individuate (especially in the case of bacteria) and hard to separate meaningfully from the cultures in which they thrive – their “goodness” or “badness” has less to do with them and more to do with the context we find them in.

Here is one thing I am comfortable saying when asked about this: If for whatever reason you are ok with letting your little boy get dirty and in the process ingesting a bunch of dirt, then the hygiene hypothesis provides you no good reason not to let your little girl do so as well.