Definitions

Hygiene_hypothesis

Hygiene hypothesis

In medicine, the hygiene hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms (e.g. gut flora), and parasites increases susceptibility to allergic diseases by modulating immune system development.

History

First proposed by David P. Strachan in an article published in the British Medical Journal (now the BMJ), in 1989, the hygiene hypothesis was developed to explain the observation that hay fever and eczema, both allergic diseases, were less common in children from larger families, which were presumably exposed to more infectious agents through their siblings, than in children from families with only one child. The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an important theoretical framework for the study of allergic disorders. It is used to explain the increase in allergic diseases that has been seen since industrialization, and the higher incidence of allergic diseases in more developed countries. The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents.

Mechanism of action

Allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a TH2-mediated immune response. Many bacteria and viruses elicit a TH1-mediated immune response, which down-regulates TH2 responses. The first proposed mechanism of action of the hygiene hypothesis stated that insufficient stimulation of the TH1 arm of the immune system lead to an overactive TH2 arm, which in turn led to allergic disease.

The first proposed mechanistic explanation for the hygiene hypothesis cannot explain the rise in incidence (similar to the rise of allergic diseases) of several TH1-mediated autoimmune diseases, including inflammatory bowel disease (IBD), multiple sclerosis (MS), and type I diabetes. The major proposed alternative mechanistic explanation is that the developing immune system must receive stimuli (from infectious agents, symbiotic bacteria, or parasites) in order to adequately develop regulatory T cells, or it will be more susceptible to autoimmune diseases and allergic diseases, because of insufficiently repressed TH1 and TH2 responses, respectively.

Breadth of the hypothesis

The hygiene hypothesis has expanded from eczema and hay fever to include exposure to several varieties of microorganisms and parasites, with which humans coexisted throughout much of our evolutionary history, as necessary for balanced and regulated immune system development. In recent times, the development of hygienic practices and effective medical care have diminished or eliminated exposure to these microorganisms and parasites during development. Examples of organisms that may be important for proper development of T regulatory cells include lactobacilli, various mycobacteria, and certain helminths.

Evidence for and against the hypothesis

Epidemiological data supports the hygiene hypothesis. 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. Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, presumably, cleaner. The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases. The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by Caesarean section rather than vaginal birth. However, the studies investigating these links showed only tenuous correlations between the factors described and the conditions they are hypothesised to cause.

Alternative hypotheses

For immunological conditions related to Strachan's original version of the hygiene hypothesis, such as atopy and asthma, the pool chlorine hypothesis was proposed by Alfred Bernard and his colleagues as an alternative hypothesis based on epidemiological evidence in 2003.

See also

References

Additional references

1. Camateros P, Moisan J, Henault J, De SJ, Skamene E and Radzioch D. Toll-like receptors, cytokines and the immunotherapeutics of asthma. Curr Pharm Des 12: 2365-2374, 2006.

External links

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