If you spend a lot of time with anti-vaxxers, you’ll notice that they tend to misuse a scientific principle, this time, the hygiene hypothesis, which is a description of how early exposure to microorganisms may assist the immune system to avoid allergic reactions to things in the environment.
Although we’ll discuss the scientific evidence in support of the hypothesis later in this article, anti-vaxxers tend to abuse it. They conflate potentially beneficial organisms, such as the gut biome, with dangerous and deadly pathogens, like measles and polio. The former may be a critical component of the hygiene hypothesis, but the latter is not.
Time to tackle this scientifically controversial topic, and put to rest one of the tropes of the anti-vaccine world that all germs are good. They aren’t.
What is the hygiene hypothesis?
The hygiene hypothesis states that a lack of early childhood exposure to certain symbiotic microorganisms, such as gut flora (sometimes called probiotics) and the microbiome, along with protozoan parasites, increases the susceptibility of the individual to allergic and autoimmune diseases. This happens because these microorganisms may enhance the development of the immune system.
Although the anti-vaccine activists abuse this hypothesis by claiming that vaccines are antithetical to the hygiene hypothesis, vaccines only induce the immune system to attack a handful of pathogens – those are microorganisms that cause a frequently deadly or dangerous disease that can be passed on to others.
The hypothesis is also known as the “biome depletion theory” and the “lost friends theory,” although those usages are not widely used by scientists.
We need to get dig into immunology a bit to understand the biological basis, and thus plausibility, of the hygiene hypothesis. Allergies are caused by unsuitable immunological responses to harmless antigens – it is driven by a TH2-mediated immune response, which is a type of T-helper cell that is critical to the adaptive immune response. Many bacteria and viruses induce a TH1-mediated immune response, which down-regulates TH2 responses. In other words, these bacteria and viruses cause the immune system to stop the allergy-causing immune responses.
An alternative explanation is that the developing immune system might be stimulated by microorganisms to develop regulatory T cells (usually called Tregs). Without that stimuli, the T helper cells aren’t properly regulated, and the immune system becomes more susceptible to autoimmune and allergic diseases. In addition, helminths (parasitic worms), non-pathogenic bacteria, or certain gut flora may drive immunoregulation. Lastly, some of these organisms may actually expand the population of Tregs or cause some of the immune systems to switch to regulatory forms that drive immunoregulation.
Once again, pathogenic bacteria and viruses, which can cause harm, including death, may also induce some of these helper cells, but at the risk of serious damage. And remember, there are thousands, if not millions, of other microorganisms that are not pathogenic that a developing immune system will encounter every single day. Preventing infections of 30-40 pathogenic microorganisms, like measles or chickenpox, are not going to have a material impact on this type of immune regulation, there are plenty of germs that a young child might encounter that will develop the immune system.
Now, you may ask why is the hygiene hypothesis a hypothesis? Simply put, a scientific hypothesis is a proposed explanation for an observed phenomenon. In this case, we have some correlation between cleaner environments, better sanitation, indoor plumbing, and purified water, and an increase in allergies and autoimmune diseases. In essence, a hypothesis is a question that can be tested to determine if it is supported or refuted by evidence derived from the scientific method.
On the scale of scientific principles, hypotheses are the first step above observations but rank far below scientific theories, which explain observations and proposed mechanisms of the natural universe that can be repeatedly tested. As you will see below, the evidence is quite mixed, so it’s hard to see the development of a scientific consensus about the hygiene hypothesis, at least in the near term.
Evidence for the hygiene hypothesis
The most powerful evidence for the hypothesis is that in areas where chronic infections by microorganisms and parasites have been eliminated or reduced, the rates of autoimmune and allergic diseases have increased. However, as I’ve written many times, correlation does not imply causation. There could be hundreds of confounding factors that could have caused the increase in autoimmune diseases from diet to air pollution to lifestyle to genetics.
The epidemiological evidence is nearly overwhelming. In study after study after study, we observe a gradient in autoimmune and allergic diseases that go from high in developed countries to low in lesser developed ones.
On the other, the biologically plausible mechanisms described above seem to be the first steps in showing causality between encountering microorganisms and parasites. The evidence in support of a causal link between the lack of microorganisms in the environment and autoimmune and allergic disorders is growing but it is limited in robustness.
Randomized, double-blind clinical trials may not be ethical, safe, or even possible. It would be difficult to ask one trial arm to intentionally ingest parasites or microorganisms that are dangerous to health. Although the data is not available, it is not hard to imagine that the risk of death or debilitation from microorganisms and parasites may be much higher than the risks attributed to immune diseases.
I am very concerned that individuals, like the anti-vaxxers, will overlook the tremendous health risk from these infectious diseases while vastly overrating the benefits that might include reducing immune disorders. Yes, areas with poor sanitation and endemic diseases may have a lower risk of immune disorders, but their lifespan is lowered as a result of these infections.
In addition, there is plenty of evidence (out of over 2500 articles published in the area) that seems to contradict the validity of the hygiene hypothesis. For example, a recent systematic review (again, considered the pinnacle of the hierarchy of biomedical scientific evidence) of the hygiene hypothesis with respect to asthma, which may be related to an allergic disorder, concluded that “present evidence that calls for caution when associating hygiene with the pathogenesis of asthma and other allergic conditions.”
Another study showed a correlation between chlorine in pools with asthma. As I mentioned above, the confounding factors, say the chlorine in swimming pools, could confuse the evidence regarding the hygiene hypothesis.
The mixed pieces of evidence are the reasons why the hygiene hypothesis isn’t known as the hygiene theory – we lack robust evidence supporting causality between hygiene and immunological disorders. In some respects, it’s not even close, though compelling in some areas.
Misuse by anti-vaxxers
I often complained that, along with being bad with science, anti-vaxxers are really bad with math. They don’t understand the whole principle of cost-benefit analyses. The hygiene hypothesis may have a powerful benefit to human immunology. However, that is balanced with a huge cost – infections, many of which are dangerous to human health, including death.
Okada et al., in a review article published in Clinical and Experimental Immunology, summarized their thoughts about how the hypothesis may be used in preventing or treating immune disorders:
The notions presented above open new, interesting, therapeutic perspectives for the prevention of allergic and autoimmune diseases. Of course, contaminating children or adults at high risk of developing these diseases by infectious agents cannot be envisioned, at a time when medical progress has allowed the reduction of major infectious diseases. It should be mentioned, however, that even if we do not believe that this is not the best strategy for the future, some groups have used living parasites such as T. suis in the prevention of IBD, as mentioned above, or living Lactobacilli in the prevention of atopic dermatitis. These approaches present the obvious limitation of insufficient standardization, and hazards linked to unpredictable disease course in subjects presenting an unknown immunodeficiency by contamination with xenogeneic virus in the case of swine-derived parasites.
The authors actually suggest that there is a better way – to isolate the allergens in these microorganisms that induce the hygiene effect. In other words, use real science to discover the biochemical allergens in the microorganism that may stimulate the immune regulatory system to prevent allergic and autoimmune diseases.
Here’s where the anti-vaxxers go off the rails (a common event) – they think that vaccines somehow violate the hygiene hypothesis. In fact, vaccines boost the immune system without dangerous infections caused by pathogens. Measles infection may slightly reduce the risk of autoimmune diseases, but that’s at the cost of a small, but statistically significant, risk of death or a deadly condition like SSPE.
The whole point of vaccines is to train the adaptive immune system to recognize the antigens on the pathogen without the dangers of infection. And if the hygiene hypothesis is to be believed, then the antigens presented in the vaccine can help induce the proper immune regulation in the same way as any wild infection.
Furthermore, a baby encounters literally millions of antigens every single day. Let’s take a look at what actually happens in the real world with children’s immune systems. In this paper, researchers discovered that:
- In each cubic meter of air, there are between 1.6 million and 40 million viruses.
- In each cubic meter of air, there are between 860,000 and 11 million bacteria.
A child inhales about 5 liters of air per minute (or about .005 cubic meters), so a few hundred thousand viruses and bacteria are inhaled every minute every day of the year by an infant. And the researchers discovered that many were unknown species of viruses and bacteria, so the immune system has to adapt to them with each breath.
Thus, the 35-40 antigens from vaccines are not even a significant number compared to the millions upon millions of viral and bacterial antigens that enter a child’s lungs every day or week. The tiny number of antigens introduced by vaccines barely register on the immune system’s massive and robust power to deal with antigens. And if the hygiene hypothesis is correct, then the vaccine-preventable diseases, which are, by definition, dangerous to human health, are a tiny drop in a huge vat of microorganisms that might induce immune regulation to prevent allergic and autoimmune disorders.
I’m not convinced of some aspects of the hygiene hypothesis, although helminth infections are intriguing as a causal factor. I also find the evidence in support of probiotics for the gut biome to be very interesting – the gut is part of the innate immune system, and it’s possible the flora of the gut may confer many benefits on the human body. However, once again, the evidence is more intriguing than convincing.
I cannot imagine living in a world where we let infectious diseases run rampant just to prevent immune disorders. There is a better way, and that’s isolating the causal antigens – that won’t be easy, but it might have the highest benefit to cost ratio.
Putting children (and adults) at risk of dangerous, and deadly, infectious diseases just to avoid some possible immune system issues may sound like a good idea. It really isn’t.
So, please ignore anti-vaccine zealots and “natural” medicine pseudoscientists who advocate having children get all the “natural” infections that are avoided by vaccines and swallow some parasites (yes, they do this). Science does not understand the hygiene hypothesis well enough at this point to even claim that it is factual — it’s a hypothesis, and it’s going to take years to determine if it really is something linked to reducing immune disorders. Science I starting to isolate factors that may be linked to increasing or reducing the risks of certain autoimmune diseases.
Give it time. Eventually, real science research will give us the answer — hopefully, it’s not swallowing a bowl of tapeworms. Count me out.
- Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002 Sep 19;347(12):911-20. Review. PubMed PMID: 12239261.
- Bernard A, Carbonnelle S, Michel O, Higuet S, De Burbure C, Buchet JP, Hermans C, Dumont X, Doyle I. Lung hyperpermeability and asthma prevalence in schoolchildren: unexpected associations with the attendance at indoor chlorinated swimming pools.Occup Environ Med. 2003 Jun;60(6):385-94. PubMed PMID: 12771389; PubMed Central PMCID: PMC1740550.
- Bresciani M, Parisi C, Menghi G, Bonini S. The hygiene hypothesis: does it function worldwide? Curr Opin Allergy Clin Immunol. 2005 Apr;5(2):147-51. doi: 10.1097/01.all.0000162307.89857.88. Erratum in: Curr Opin Allergy Clin Immunol. 2005 Jun;5(3):307. Manghi, Ginevra [corrected to Menghi, Ginevra]. PMID: 15764905.
- Jafari AA, Keikha M, Mirmoeeni S, Rahimi MT, Jafari R. Parasite-based interventions in systemic lupus erythematosus (SLE): A systematic review. Autoimmun Rev. 2021 Oct;20(10):102896. doi: 10.1016/j.autrev.2021.102896. Epub 2021 Jul 15. PMID: 34274545.
- Kramer A, Bekeschus S, Bröker BM, Schleibinger H, Razavi B, Assadian O. Maintaining health by balancing microbial exposure and prevention of infection: the hygiene hypothesis versus the hypothesis of early immune challenge. J Hosp Infect. 2013 Feb;83 Suppl 1:S29-34. doi: 10.1016/S0195-6701(13)60007-9. Review. PubMed PMID: 23453173.
- Okada H, Kuhn C, Feillet H, Bach JF. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010 Apr;160(1):1-9. doi: 10.1111/j.1365-2249.2010.04139.x. Review. PubMed PMID: 20415844; PubMed Central PMCID: PMC2841828.
- Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, Mazmanian SK. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science. 2011 May 20;332(6032):974-7. doi: 10.1126/science.1206095. Epub 2011 Apr 21. PubMed PMID: 21512004; PubMed Central PMCID: PMC3164325.
- Smits HH, Engering A, van der Kleij D, de Jong EC, Schipper K, van Capel TM, Zaat BA, Yazdanbakhsh M, Wierenga EA, van Kooyk Y, Kapsenberg ML. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol. 2005 Jun;115(6):1260-7. PubMed PMID: 15940144.
- Symmons DP. Frequency of lupus in people of African origin. Lupus. 1995 Jun;4(3):176-8. PubMed PMID: 7655486.
- van Tilburg Bernardes E, Arrieta MC. Hygiene Hypothesis in Asthma Development: Is Hygiene to Blame? Arch Med Res. 2017 Nov;48(8):717-726. doi: 10.1016/j.arcmed.2017.11.009. Epub 2017 Dec 7. Review. PubMed PMID: 29224909.
- Whon TW, Kim MS, Roh SW, Shin NR, Lee HW, Bae JW. Metagenomic characterization of airborne viral DNA diversity in the near-surface atmosphere. J Virol. 2012 Aug;86(15):8221-31. doi: 10.1128/JVI.00293-12. Epub 2012 May 23. PubMed PMID: 22623790; PubMed Central PMCID: PMC3421691.
- Yang Z, Wang K, Li T, Sun W, Li Y, Chang YF, Dorman JS, LaPorte RE. Childhood diabetes in China. Enormous variation by place and ethnic group. Diabetes Care. 1998 Apr;21(4):525-9. PubMed PMID: 9571336.
- Review of the book “We Want Them Infected” by Jonathan Howard - 2023-11-28
- Flu vaccine reduces heart attacks - 2023-11-27
- Thanksgiving dinner and sleep — don’t blame tryptophan in turkey - 2023-11-21