From Amish farm dust to bacterial lysates: The long and winding road to protection from allergic disease

Allergic diseases typically begin in early life and can impose a heavy burden on children and their families. Effective preventive measures are currently unavailable but may be ushered in by studies on the "farm effect", the strong protection from asthma and allergy found in children born and raised on traditional farms. Two decades of epidemiologic and immunologic research have demonstrated that this protection is provided by early and intense exposure to farm-associated microbes that target primarily innate immune pathways. Farm exposure also promotes timely maturation of the gut microbiome, which mediates a proportion of the protection conferred by the farm effect. Current research seeks to identify allergy-protective compounds from traditional farm environments, but standardization and regulation of such substances will likely prove challenging. On the other hand, studies in mouse models show that administration of standardized, pharmacological-grade lysates of human airway bacteria abrogates allergic lung inflammation by acting on multiple innate immune targets, including the airway epithelium/IL-33/ILC2 axis and dendritic cells whose Myd88/Trif-dependent tolerogenic reprogramming is sufficient for asthma protection in adoptive transfer models. To the extent that these bacterial lysates mimic the protective effects of natural exposure to microbe-rich environments, these agents might provide an effective tool for prevention of allergic disease.