Hygiene hypothesis
In medicine, the hygiene hypothesis states that early childhood exposure to particular microorganisms (such as the
While early versions of the hypothesis referred to microorganism exposure in general, later versions apply to a specific set of microbes that have
The term "hygiene hypothesis" has been described as a misnomer because people incorrectly interpret it as referring to their own cleanliness.
Overview
The idea of a link between parasite infection and immune disorders was first suggested in 1968
The hygiene hypothesis has also been expanded beyond allergies, and is also studied in the context of a broader range of conditions affected by the immune system, particularly
In 2003, Graham Rook proposed the "old friends" hypothesis which has been described as a more rational explanation for the link between microbial exposure and inflammatory disorders.[20] The hypothesis states that the vital microbial exposures are not colds, influenza, measles and other common childhood infections which have evolved relatively recently over the last 10,000 years, but rather the microbes already present during mammalian and human evolution, that could persist in small hunter-gatherer groups as microbiota, tolerated latent infections, or carrier states. He proposed that coevolution with these species has resulted in their gaining a role in immune system development.[citation needed]
Strachan's original formulation of the hygiene hypothesis also centred around the idea that smaller families provided insufficient microbial exposure partly because of less person-to-person spread of infections, but also because of "improved household amenities and higher standards of personal cleanliness".
The rise of
History
Since allergies and other chronic inflammatory diseases are largely diseases of the last 100 years or so, the "hygiene revolution" of the last 200 years came under scrutiny as a possible cause. During the 1800s, radical improvements to sanitation and water quality occurred in Europe and North America. The introduction of toilets and sewer systems and the cleanup of city streets, and cleaner food were part of this program. This in turn led to a rapid decline in infectious diseases, particularly during the period 1900–1950, through reduced exposure to infectious agents.[21]
Although the idea that exposure to certain infections may decrease the risk of allergy is not new, Strachan was one of the first to formally propose it, in an article published in the
The "old friends hypothesis" proposed in 2003
Rook proposed that these microbes most likely include:
- Ambient species that exist in the same environments as humans
- Species that inhabit human skin, gut and respiratory tract, and that of the animals we live with
- Organisms such as helminths(worms) that establish chronic infections or carrier states that humans can tolerate and so could co-evolve a specific immunoregulatory relationship with the immune system.
The modified hypothesis later expanded to include exposure to
"Evolution turns the inevitable into a necessity." This means that the majority of mammalian evolution took place in mud and rotting vegetation and more than 90 percent of human evolution took place in isolated hunter-gatherer communities and farming communities. Therefore, the human immune systems have evolved to anticipate certain types of microbial input, making the inevitable exposure into a necessity. The organisms that are implicated in the hygiene hypothesis are not proven to cause the disease prevalence, however there are sufficient data on lactobacilli, saprophytic environment mycobacteria, and helminths and their association. These bacteria and parasites have commonly been found in vegetation, mud, and water throughout evolution.[18][20]
Multiple possible mechanisms have been proposed for how the 'Old Friends' microorganisms prevent autoimmune diseases and asthma. They include:
- Reciprocal inhibition between immune responses directed against distinct antigens of the Old Friends microbes which elicit stronger immune responses than the weaker autoantigens and allergens of autoimmune disease and allergy respectively.
- Competition for cytokines, MHC receptors and growth factors needed by the immune system to mount an immune response.
- Immunoregulatory interactions with host TLRs.[23]
The "microbial diversity" hypothesis, proposed by Paolo Matricardi and developed by von Hertzen,
For allergic disease, the most important times for exposure are: early in development; later during pregnancy; and the first few days or months of infancy. Exposure needs to be maintained over a significant period. This fits with evidence that delivery by Caesarean section may be associated with increased allergies, whilst breastfeeding can be protective.[21]
Evolution of the adaptive immune system
Humans and the microbes they harbor have co-evolved for thousands of centuries; however, it is thought that the human species has gone through numerous phases in history characterized by different pathogen exposures. For instance, in very early human societies, small interaction between its members has given particular selection to a relatively limited group of pathogens that had high transmission rates. It is considered that the human immune system is likely subjected to a selective pressure from pathogens that are responsible for down regulating certain alleles and therefore phenotypes in humans. The thalassemia genes that are shaped by the Plasmodium species expressing the selection pressure might be a model for this theory[33] but is not shown in-vivo.
Recent comparative genomic studies have shown that immune response genes (protein coding and non-coding regulatory genes) have less evolutionary constraint, and are rather more frequently targeted by positive selection from pathogens that coevolve with the human subject. Of all the various types of pathogens known to cause disease in humans, helminths warrant special attention, because of their ability to modify the prevalence or severity of certain immune-related responses in human and mouse models. In fact recent research has shown that parasitic worms have served as a stronger selective pressure on select human genes encoding interleukins and interleukin receptors when compared to viral and bacterial pathogens. Helminths are thought to have been as old as the adaptive immune system, suggesting that they may have co-evolved, also implying that our immune system has been strongly focused on fighting off helminthic infections, insofar as to potentially interact with them early in infancy. The host-pathogen interaction is a very important relationship that serves to shape the immune system development early on in life.[34][35][36][37]
Biological basis
The primary proposed mechanism of the hygiene hypothesis is an imbalance between the TH1 and TH2 subtypes of T helper cells.[10][38] Insufficient activation of the TH1 arm would stimulate the cell defense of the immune system and lead to an overactive TH2 arm, stimulating the antibody-mediated immunity of the immune systems, which in turn led to allergic disease.[39]
However, this explanation cannot explain the rise in incidence (similar to the rise of allergic diseases) of several TH1-mediated
Allergic conditions are caused by inappropriate immunological responses to harmless
An alternative explanation is that the developing immune system must receive stimuli (from infectious agents, symbiotic bacteria, or parasites) to adequately develop
Evidence
There is a significant amount of evidence supporting the idea that microbial exposure is linked to allergies or other conditions,[2][6][7] although scientific disagreement still exists.[4][8][9] Since hygiene is difficult to define or measure directly, surrogate markers are used such as socioeconomic status, income, and diet.[38]
Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world.[23] This is true for asthma and other chronic inflammatory disorders.[18] The increase in allergy rates is primarily attributed to diet and reduced microbiome diversity, although the mechanistic reasons are unclear.[45]
The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases,[46] and increased asthma rates are also associated with birth by Caesarean section.[47] However, at least one study suggests that personal hygienic practices may be unrelated to the incidence of asthma.[9] Antibiotic usage reduces the diversity of gut microbiota. Although several studies have shown associations between antibiotic use and later development of asthma or allergy, other studies suggest that the effect is due to more frequent antibiotic use in asthmatic children. Trends in vaccine use may also be relevant, but epidemiological studies provide no consistent support for a detrimental effect of vaccination/immunization on atopy rates.[21] In support of the old friends hypothesis, the intestinal microbiome was found to differ between allergic and non-allergic Estonian and Swedish children (although this finding was not replicated in a larger cohort), and the biodiversity of the intestinal flora in patients with Crohn's disease was diminished.[23]
Limitations
The hygiene hypothesis does not apply to all populations.[9][38] For example, in the case of inflammatory bowel disease, it is primarily relevant when a person's level of affluence increases, either due to changes in society or by moving to a more affluent country, but not when affluence remains constant at a high level.[38]
The hygiene hypothesis has difficulty explaining why allergic diseases also occur in less affluent regions.[9] Additionally, exposure to some microbial species actually increases future susceptibility to disease instead, as in the case of infection with rhinovirus (the main source of the common cold) which increases the risk of asthma.[4][48]
Treatment
Current research suggests that manipulating the intestinal microbiota may be able to treat or prevent allergies and other immune-related conditions.
Should these therapies become accepted, public policy implications include providing green spaces in urban areas or even providing access to agricultural environments for children.[50]
Public health
The reduction of public confidence in hygiene has significant possible consequences for public health.
The misunderstanding of the term "hygiene hypothesis" has resulted in unwarranted
Cleanliness
No evidence supports the idea that reducing modern practices of cleanliness and hygiene would have any impact on rates of chronic inflammatory and allergic disorders, but a significant amount of evidence indicates that reducing hygiene would increase the risks of infectious diseases.[21] The phrase "targeted hygiene" has been used in order to recognize the importance of hygiene in avoiding pathogens.[1]
If home and personal cleanliness contributes to reduced exposure to vital microbes, its role is likely to be small. The idea that homes can be made “sterile” through excessive cleanliness is implausible, and the evidence shows that after cleaning, microbes are quickly replaced by dust and air from outdoors, by shedding from the body and other living things, as well as from food.[21][56][57][58] The key point may be that the microbial content of urban housing has altered, not because of home and personal hygiene habits, but because they are part of urban environments. Diet and lifestyle changes also affects the gut, skin and respiratory microbiota.[citation needed]
At the same time that concerns about allergies and other chronic inflammatory diseases have been increasing, so also have concerns about infectious disease.
Infection risk management
The International Scientific Forum on Home Hygiene has developed a risk management approach to reducing home infection risks. This approach uses microbiological and epidemiological evidence to identify the key routes of infection transmission in the home. These data indicate that the critical routes involve the hands, hand and food contact surfaces and cleaning utensils. Clothing and household linens involve somewhat lower risks. Surfaces that contact the body, such as baths and hand basins, can act as infection vehicles, as can surfaces associated with toilets. Airborne transmission can be important for some pathogens. A key aspect of this approach is that it maximises protection against pathogens and infection, but is more relaxed about visible cleanliness in order to sustain normal exposure to other human, animal and environmental microbes.[56]
See also
- Antibacterial soap
- Antifragility
- Diseases of affluence
- Germ theory of disease
- Helminthic therapy
- Hookworm
- Human microbiome
- Microbiomes of the built environment
- Vaginal seeding
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Further reading
- Dunn, Rob (2018). Never Home Alone: From Microbes to Millipedes, Camel Crickets, and Honeybees, the Natural History of Where We Live. Basic Books. ISBN 978-1541645769.
- Finlay, B. Brett; Arrieta, Marie-Claire (2016). Let Them Eat Dirt. Algonquin Books. ISBN 978-1616207380.
- Hadley, Caroline (December 2004). "Should auld acquaintance be forgot…". EMBO Reports. 5 (12): 1122–1124. PMID 15577925.
- Rook, G A W; Brunet, LR (1 March 2005). "Microbes, immunoregulation, and the gut". Gut. 54 (3): 317–320. PMID 15710972.
- Rook, G. A. W.; Adams, V.; Palmer, R.; Brunet, L. Rosa; Hunt, J.; Martinelli, R. (1 February 2004). "Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders". Springer Seminars in Immunopathology. 25 (3–4): 237–255. S2CID 11393930.