Allergy: the price we pay for cleaner living?

There is an urgent need to identify the environmental changes responsible for the increasing burden of allergic disease. A reduction in the diversity and magnitude of "microbial burden" in early life has been implicated in this growing propensity for allergy sensitization. The "hygiene hypothesis" proposes that deficient bacteria-derived maturation signals during early immune development increases the susceptibility to allergic responses. This article reviews the current evidence for this relationship in the context of improved public health and living conditions.

Evidence derived from a wide range of epidemiologic and intervention studies in humans and experimental animal models is reviewed.

There is extensive epidemiologic evidence linking allergic disease with a number of lifestyle factors that may reflect reduced microbial burden. These studies cannot exclude other possible causal pathways because most parameters (such as family size) are only indirect measures of early childhood infection. However, direct evidence that bacteria can inhibit allergic immune responses provides a plausible mechanistic basis for the hygiene hypothesis. In both animals and humans, microbial antigens can promote nonallergic (type 1) responses and inhibit allergic (type 2) immune responses. These pro-type 1 effects have been used in allergen immunotherapy and other treatments for allergic disease with some success. Although the potential benefits of bacterial exposure appear most relevant in early life when immune responses develop, the role in disease prevention remains controversial. Furthermore, there is currently no evidence that existing childhood vaccine programs to prevent serious infectious disease are responsible for the increase in allergic disease.

Although microbial antigens can inhibit allergic immune responses, these effects appear to depend on the timing of exposure, the genetic susceptibility of the individual, the nature of the organism, and other poorly defined factors in prevailing environment. Although there is indirect support for the hygiene hypothesis, there is currently no definitive proof that reduced microbial burden is the cause of the current "allergy epidemic."