Last year we celebrated the 30th anniversary of the Hygiene Hypothesis. Starting with the simple observation that frequent microbes or parasites infections in childhood are inversely associated with allergic diseases, this theory postulates that minor hygiene conditions are responsible for this phenomenon. Based on this assumption the more specific “Old Friends-Hypothesis” lines out that infections acquired early in childhood might educate the developing immune system from Th2-dominated in utero-milieu towards a more defensive Th1-response, thus protecting against allergic diseases. Thereby, the Hygiene Hypothesis was anchored on an immunological fundament.

Since then, several studies following the hygiene hypothesis showed different results, revealing that the theory had significant gaps. For example, the association between atopic diseases and parasitic infections has been shown to have a direct or indirect relationship in human populations, with some helminths acting both as risk (e.g., Ascaris, Anisakis or Toxocara) or protective factors (e.g., Schistosoma mansoni and hookworms) for the onset of atopy and/or asthma. This depends on the helminth species, the epidemiology, the host genetics and the parasite burden. This is why other factors have been proposed to fill these gaps and provide an explanation for the conflicting effects of parasites infection on allergy development. Among these, the gut microbiota have been found to have an outstanding role in allergic disease, acting as strong influencers of the immunological competencies of the host. The modern lifestyle, particularly indoor activities, also plays a fundamental role in allergy development. In fact, the bacterial composition of the so called “indoor microbiota” could prevent or stimulate the development of airway inflammation and asthma, depending on if it is clean or burdened with moisture and molds, respectively. On this line, a number of studies emphasized the role of pollution and environmental exposures to CO2 emissions in relation to allergic outcome. Together with this, in the past years, the discovering mechanisms of epigenetic modifications as DNA-methylation, histone-modification and, at the cellular level, micro-RNA regulation, opened up an exciting new field of research covering the role of epigenetic modifications in allergy development. Finally, there is an ongoing debate about whether there are clinically definable asthma phenotypes and how they can be explained by the hygiene hypothesis. The use of new animal models based on a more flexible administration of the allergens, together with advanced statistical methods, pointed out the existence of such distinct phenotypes in asthma development and paved the way to better prediction of persistent asthma.

In this Research Topic, we aim to provide a comprehensive overview of the current advances in the study of Hygiene Theory, focusing on genetics and environmental factors able to control host immune system’s pathways and components leading to allergy and asthma development. We welcome Original Research, Reviews, Hypothesis and Theory articles, covering the following subtopics related to the Hygiene Hypothesis:

• Helminth parasites and allergy
• The role of genetics and epigenetics in allergy development
• Correlation between gut-microbiota and the immune competence of the host
• The impact on environmental factors, including pollution, indoor air and urban lifestyle on allergy outcome
• The role of Hygiene Hypothesis in the onset of different asthma phenotypes

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