Overview: The paradox of microbial impact on the immune system in allergy prevention and exacerbation

Allergy prevalence has been increasing to epidemic proportions. The term “allergy tsunami” was even coined after the prevalence of allergen sensitization in school-aged children jumped to more than 40%. Because of the huge economic impact on the health care system and the dramatic impact on quality of life, allergy prevention has become very relevant. In this context, it is interesting that infectious diseases are becoming less prevalent and increasingly under control, while noncommunicable diseases (including, but not limited to, allergy) increase. This also applies to autoimmune diseases, which are characterized by an overactive immune response. The immune system’s response to antigens and the microbiome is critical for the outcome of infections and allergies. Paradoxically, the microbiome can play a protective role in allergies, but it is also known to be the driver of exacerbations. The current chapter focuses on this paradox and therefore starts with the topic of autoallergy, in which microbial antigens are considered to be potential pathogens and disease initiators. Bacterial allergens are generally thought of as potential “virulence factors” and exacerbation factors in allergy. In contrast, the allergy-protective microbiome, which was discovered in protective agricultural environments, is the second key aspect of this chapter. Additional environmental elements that were lost due to lifestyle changes are also highlighted. Both farm and lifestyle effects contributed to the hygiene hypothesis, which is challenged by the author to show that “dirt” is not at all protective against allergies. Determinants and metabolites of bacteria and molds that co-evolutionized with man have been identified in rural environments, with stunning effects on our immune systems. Allergy prevention at least partially develops in our gut through a complex interplay of microbiota with our immune system. Here, the persistence of type-2 allergen memory, such as interleukin-4 and immunoglobulin E–producing cells, is particularly important and relevant for food allergies. This chapter also describes a recently discovered mechanism that links the gut microbiome with pro-allergic type-2 immunity. The mechanism of environmental sensing is discussed, using the example of the aryl hydrocarbon receptor to demonstrate the link between microbiota, their metabolites, and their recognition at cellular and molecular levels. For the prevention of microbiome-driven exacerbations, the chapter also discusses therapeutic options with novel diagnostics and biologics that are likely to influence the future management of allergies. (For a graphical chapter overview, see Fig. 1.).