Hygiene hypothesis and endotoxin: what is the evidence?

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Abstract
The hygiene hypothesis has gained strong support over the past few years. Exposure to microbial products in early life could be an underlying factor in this hypothesis, but the mechanisms that lead from a less clean and more crowded environment to a lower prevalence of asthma and allergies are not known. Among the variety of potential microbial molecules that may confer protection against the development of asthma and allergies, endotoxin, a component of Gram-negative bacteria, has incited lively as well as controversial discussions. This review focuses on recent studies on endotoxin and its role in the context of the hygiene hypothesis. Results from cross-sectional surveys, prospective cohorts, and experimental studies in vitro and in rodents suggest that exposure to house dust endotoxin in early life protects from atopic sensitization and IgE-mediated diseases, but is a risk factor for wheezing in infancy. Numerous studies have supported the hygiene hypothesis, but whether endotoxin by itself confers the protection or whether it acts as a marker for another environmental exposure is still unclear. The challenge for the future will be to identify those factors that confer the protection proposed by the hygiene hypothesis, and to find strategies to modify the environment without causing harm to susceptible individuals.