Predictors and biomarkers of food allergy and sensitization in early childhood

Abstract

Objective: To review existing literature on the early risk factors for and biomarkers of food allergy (FA) and food sensitization (FS) and highlight opportunities for future research that will further the understanding of FA pathogenesis in infancy and toddlerhood.

Data sources: PubMed search of English-language articles related to FA and atopic disease.

Study selections: Human studies with outcomes related to FA, FS, and other atopic disease in childhood were selected and reviewed. Studies published after 2015 were prioritized.

Results: The prevalence of FA has greatly increased in recent decades and is now a global public health concern. A complex network of early life risk factors has been associated with development of FA and FS in childhood. Food allergy has a genetic component, but recent evidence suggests that interactions between risk alleles and other environmental exposures are important for disease pathogenesis, potentially through epigenetic mechanisms. Lifestyle factors, such as delivery mode, antibiotic use, and pet exposure also influence FA risk, which may be through their effect on the early life gut microbiome. How these early life risk factors, along with route and timing of antigen exposure, collectively target the developing immune system remains an ongoing and important area of study.

Conclusion: The current body of evidence emphasizes the first 1000 days of life as a critical period for FA development. More observational studies and adequately powered clinical trials spanning early pregnancy through childhood are needed to identify novel biomarkers and risk factors that can predict susceptibility toward or protection against FA.

Figure 1.. Routes of infant allergen exposure.

In utero, food antigens may be transplacentally delivered to the fetus. After birth, infants can be exposed to food allergens through human milk or infant formula and eventually through their diet. Throughout these periods, individuals may also be exposed to allergens through their environment.

Figure 2.. Early life risk factors and targets that influence susceptibility to food allergy.

Genetics, animal exposures, family size, breastfeeding, and early allergen exposure are associated with food allergy risk. These factors are hypothesized to influence risk through effects on the microbiome, metabolome, and the developing immune system, potentially through epigenetic mechanisms.