What is the role of bacterial exposure in asthma protection and prevention? This topic is receiving increasing attention, particularly based on epidemiological findings relating to the ‘hygiene hypothesis’. More than a decade ago the observation was made that infants living in a microbial-rich environment show a high degree of protection, particularly against respiratory allergies and allergic sensitisation.1 The model situation of the farming environment offers the opportunity to investigate the context of environmental exposures, the effect on immune responses and development of disease phenotypes. That microbes are indeed relevant in triggering the protective immune response was epidemiologically shown initially for exposure to lipopolysaccharide (LPS), a membrane component of Gram-negative bacteria. In that study, an inverse relationship was observed between the natural microbial load (endotoxin load in mattress dust) and the prevalence of asthma, allergic rhinitis and atopic sensitisation. Subsequently, several groups employed models of experimental asthma to study the mechanisms of protection in this regard.2–4 These studies provided important information for the context of microbial exposure and asthma protection. First, it was shown that timing of exposure is relevant. If LPS was delivered well before the first contact with the allergen, the immune system was able …