Early life microbial exposures and allergy risks: opportunities for prevention

Abstract

Allergies, including asthma, food allergy and atopic dermatitis, are increasing in prevalence, particularly in westernized countries. Although a detailed mechanistic explanation for this increase is lacking, recent evidence indicates that, in addition to genetic predisposition, lifestyle changes owing to modernization have an important role. Such changes include increased rates of birth by caesarean delivery, increased early use of antibiotics, a westernized diet and the associated development of obesity, and changes in indoor and outdoor lifestyle and activity patterns. Most of these factors directly and indirectly impact the formation of a diverse microbiota, which includes bacterial, viral and fungal components; the microbiota has a leading role in shaping (early) immune responses. This default programme is markedly disturbed under the influence of environmental and lifestyle risk factors. Here, we review the most important allergy risk factors associated with changes in our exposure to the microbial world and the application of this knowledge to allergy prevention strategies.

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Fig. 1: Caesarean delivery is an important risk factor for the development of chronic immune and metabolic disease.
Fig. 2: Prenatal and postnatal risk factors for the development of allergy and asthma.
Fig. 3: Reciprocal negative regulation of type I and III interferons and TH2-type responses in patients with asthma.
Fig. 4: The concept of inflammatory resilience.

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Acknowledgements

H.R. is supported by the Universities of Giessen and Marburg Lung Center, the German Center for Lung Research (82DZL00502/A2), and the Deutsche Forschungsgemeinschaft funded-SFB 1021 (C04). C.S. is supported by the Universities of Giessen and Marburg Lung Center, the German Center for Lung Research, University Hospital of Giessen and Marburg research funding according to article 2, section 3 cooperation agreement, the Foundation for Pathobiochemistry and Molecular Diagnostics, and the Deutsche Forschungsgemeinschaft-funded SFB 1021 (C04), KFO 309 (P10) and SK 317/1-1 (project number 428518790).

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C.S. wrote and edited the manuscript. H.R. helped revise and edit the manuscript.

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Correspondence to Harald Renz.

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C.S. has received consultancy fees and research funding from Hycor Biomedical and Thermo Fisher Scientific, consultancy fees from Bencard Allergie and research funding from Mead Johnson Nutrition. H.R. has received research support from Mead Johnson Nutrition and Beckman Coulter, has received speaker’s honoraria from Allergopharma, Novartis, Thermo Fisher, Danone, Mead Johnson Nutrition and Bencard Allergie, and has been a consultant for Bencard Allergie and Secarna Pharmaceuticals (co-founder).

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Nature Reviews Immunology thanks K. C. Nadeau, V. Verhass and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Centers for Disease Control and Prevention: most recent asthma data: https://www.cdc.gov/asthma/most_recent_data.htm

Glossary

Short-chain fatty acids

(SCFAs). Subgroup of fatty acids with only two to six carbon atoms. Important representatives are butyrate, acetate and propionate.

Dysbiosis

A condition in which there is a qualitative and quantitative imbalance of bacterial communities that constitute the microbiota, which could represent a predisposition factor for several diseases. Dysbiosis refers mostly to the intestinal microbiota, but it can also occur at other body sites and in other habitats.

Human milk oligosaccharides

(HMOs). Complex sugar molecules that are present in human breast milk in relatively high concentrations; their composition shows high interindividual and intraindividual variability.

Group 2 innate lymphoid cells

(ILC2s). Derived from lymphoid progenitors, these cells lack B and T cell receptors and produce type 2 cytokines such as IL-4, IL-5 and IL-9

Inflammasome

Cytosolic multiprotein oligomer of the innate immune system responsible for the activation of the inflammatory responses.

Asthma endotypes

Forms of asthma with distinct mechanistic pathways that have therapeutic and prognostic implications.

Neutrophil extracellular traps

Networks of extracellular fibres, produced by neutrophils, which bind to pathogens and thus allow neutrophils to kill them with minimal host damage. The extracellular fibril matrix is composed of decondensed chromatin.

Plasmacytoid dendritic cell

Derived from bone marrow haematopoietic stem cells, this type of immune cell circulates in the blood and in peripheral lymphoid organs and is known to secrete large quantities of type I interferon following viral infection.

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Renz, H., Skevaki, C. Early life microbial exposures and allergy risks: opportunities for prevention. Nat Rev Immunol (2020). https://doi.org/10.1038/s41577-020-00420-y

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