The farm effect, or: When, what and how a farming environment protects from asthma and allergic disease

Purpose of review: Multiple studies have shown that the prevalence of asthma and atopy is reduced in children raised on traditional dairy farms. This article discusses the temporal constraints for the protective farm effect, the components of a farming environment that are associated with protection, and novel mechanisms that may underlie protection from asthma and atopy in farming populations. Recent finding: Protection from asthma and allergy is strongest when exposure occurs in utero or early in life, but the protective effects can persist into adulthood. Just three exposures (contact with cows and straw and consumption of unprocessed cow's milk) account for virtually all the protective farm effect for asthma but not atopy. Whey proteins appear to be critical for the protective effects of farm milk, whereas the high microbial diversity existing in a farm environment is strongly and inversely associated with asthma, but only weakly associated with atopy. Therefore, distinct mechanisms are likely to mediate protection from asthma and atopy. The biological significance of microbial diversity is still unclear, but multiple lines of evidence link the asthma-protective and allergy-protective effects of farming to immune responses and the microbiome. Work in mouse models is revealing novel cellular and molecular mechanisms through which the microbiota may modulate immune responses and allergic inflammation, and thus contribute to the farm effect. The role of the host's genetic makeup, on the contrary, remains poorly understood. Summary: The discovery of the central role played by microbial diversity in the asthma-protective and allergy-protective effects of farming warrants metagenomic studies that concertedly and longitudinally investigate the microbiome, the genome, and the immune system of farmers and the farms they live on.