Environmental and occupational respiratory disorders
Disconnection of man and the soil: Reason for the asthma and atopy epidemic?

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Intense search has been going on to find factors responsible for the asthma and atopy epidemic in Western societies. Attention has increasingly been devoted to environmental saprophytes, which, in addition to gut commensals, might be the major players in the development and fine tuning of immunologic homeostasis. This review outlines current evidence for the role of environmental saprophytes in the development of atopic disease and considers the consequences of urbanization in reducing contacts with soil microorganisms. The major microbial components that have been shown to possess immunomodulatory capacity and their respective Toll-like receptors are also discussed, as are the possible mechanisms underlying the ability of saprophytes to confer protection against atopic disease.

Section snippets

Hypothesis

In this review we propose a hypothesis that one major factor in the current asthma and atopy epidemic might be the disconnection of man and the soil.

Evidence to support the hypothesis

There is abundant literature on adverse respiratory health effects attributable to exposure to environmental bioparticles (eg, bacteria, molds, and fugal spores).22 Paradoxically, data are now accumulating to suggest that exposure to microbes in soil and vegetation might be beneficial, even necessary, for the normal maturation of the immune system.

Several lines of evidence indicate that settings associated with high-level exposure to microorganisms in soil are associated with reduced risk for

Soil microbiota

Soil is considered the most complicated biomaterial and at the same time the most diverse and important ecosystem on the planet.49 The definition of the microbial composition of a typical soil has proved to be problematic because of this diversity of soil types and the complexity and variability of the physicochemical circumstances. Nonetheless, the majority of soil bacteria are considered to belong to the lineage of gram-positive bacteria,50 and members of the phylum Actinobacter have been

Major components of microorganisms with immunomodulatory potential and their interaction with the innate immunity

The idea that microbial products have immunomodulatory potential and could be used as immunotherapeutic agents in asthma and allergies dates back to the 1950s.61 Bacterial extracts obtained mainly from species associated with upper respiratory tract and urinary tract infections administered subcutaneously were earlier used for such purposes but are not in use today because several double-blind studies showed no efficacy in asthma, possibly because of overly low concentrations of bacterial

Tolerance and Treg cells

Repeated or persistent exposure appears to be one fundamental factor in the induction of tolerance. Repeated intranasal antigen exposure leads to decreased bronchial reactivity and tolerance in TH2-sensitized mice.105, 106 In addition, allergen desensitization therapy (injection of a specific allergen extract at increasing doses) has for years been successfully used, particularly in patients with hay fever and insect venom allergy.107 Tolerance is mediated by several mechanisms, including

TLRs and gene-environment interaction

Innate immunity is now recognized as a central element also in the gene-environment interaction. The significance of particularly the TLR2 gene in this respect has been demonstrated in several studies. In European children TLR2 gene expression has been found to be higher in blood cells obtained from farmers' children compared with that seen in children not growing up on a farm. A similar difference was not found for the TLR4 gene.114 Furthermore, a genetic variation in the TLR2 gene was shown

Concluding remarks

Several lines of evidence support the view that the environment in modern industrialized societies is unable to provide the stimulation for the developing immune system that might be beneficial or even necessary: disruption of the ancient connection of humankind and the soil might have had unexpected consequences.

The immunomodulatory role of saprophytic bacteria in soil and vegetation is now increasingly recognized. The innate immune system recognizes such saprophytes or their nonviable

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    Supported by the Academy of Finland (grant no. 201246), by Helsinki University Hospital Grants (no. 2250 and 5201), and by the Finnish Anti-Tuberculosis Association Foundation.

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