Demystifying Dysbiosis: Can the Gut Microbiome Promote Oral Tolerance Over IgE-mediated Food Allergy?

ABSTRACT

The growing burden of food allergy is being driven by environmental exposures and the potential role of gut micro-organisms (or 'microbiota') is hotly debated. Early culture-based studies outlined that imbalances between commensal gut constituents ('dysbiosis') early in life may raise the risk of developing allergic disease. A number of studies using animal models describe mechanisms by which specific bacterial taxa within the gut microbiota, their diversity and dietary substrates such as fibre may promote oral tolerance. Next-generation sequencing now allows the detailed characterization of the microbiota in relation to epidemiological exposures and clinical food allergy status in humans. Faecal samples from one birth cohort characterized for food allergy status have been sequenced and showed less gut microbiota richness amongst three month infants who later developed food sensitization at one year. A large cross-sectional survey of young children with milk allergy showed that greater gut microbiota diversity and enrichment of Clostridia and Firmicutes phyla during early infancy is associated with greater likelihood of out-growing milk allergy by eight years of age. Case control studies are limited to selecting participants from amongst hospital patients and have only allowed comparison of heterogeneous groups. To assess whether infants' gut microbiota may predispose towards the development of food allergy, cohort studies must be undertaken to evaluate gut microbiota development from early in infancy and prospectively characterise patterns according to whether challenge proven food allergy later develops, whilst adjusting for atopic dermatitis, dietary and antibiotic exposures.