Immunological resilience and biodiversity for prevention of allergic diseases and asthma

Future research perspectives • Knowledge of the determinants of immunological resilience is a prerequisite for primary prevention. • Controlled and real-world interventions to study both mechanisms and clinical effect of biodiversity. • Functional capacity of the microbiome, what are the decisive factors: richness, diversity, or composition? • Transfer of microbiota from the environment to human body. • Interaction of epigenetic markers with human or environmental microbiota. • Validation of the cellular effects of biogenic (volatile, organic) compounds in clinical setting. Milestones • Recognition of human body as a community of species (holobiont) and genomes (hologenome). • Insight of epigenetic regulation of immune adaptation under continuous environmental pressure. • Biodiversity hypothesis of health. Recognition biodiversity as a major determinant of human health (WHO, The Convention on Biological Diversity 2015). • Evidence-based nature/biodiversity loss, verified by a long-term follow-up (WWF, Living Planet Index 1970–2020). • Concept of Planetary Health as the health of human civilization and the state of natural systems (The Rockefeller Foundation-Lancet Commission 2015). • Paradigm shift in allergy prevention, from avoidance to immunological tolerance/resilience. Implementation of the first national programme for prevention (The Finnish Allergy Programme 2008–2018).Increase of allergic conditions has occurred at the same pace with the Great Acceleration, which stands for the rapid growth rate of human activities upon earth from 1950s. Changes of environment and lifestyle along with escalating urbanization are acknowledged as the main underlying causes. Secondary (tertiary) prevention for better disease control has advanced considerably with innovations for oral immunotherapy and effective treatment of inflammation with corticosteroids, calcineurin inhibitors, and biological medications. Patients are less disabled than before. However, primary prevention has remained a dilemma. Factors predicting allergy and asthma risk have proven complex: Risk factors increase the risk, while protective factors counteract them. Interaction of human body with environmental biodiversity with micro-organisms and biogenic compounds as well as the central role of epigenetic adaptation in immune homeostasis have given new insight. Allergic diseases are good indicators of the twisted relation to environment. In various non-communicable diseases, the protective mode of the immune system indicates low-grade inflammation without apparent cause. Giving microbes, pro- and prebiotics, has shown some promise in prevention and treatment. The real-world public health programme in Finland (2008–2018) emphasized nature relatedness and protective factors for immunological resilience, instead of avoidance. The nationwide action mitigated the allergy burden, but in the lack of controls, primary preventive effect remains to be proven. The first results of controlled biodiversity interventions are promising. In the fast urbanizing world, new approaches are called for allergy prevention, which also has a major cost saving potential