Gut microbiome in the first 1000 days and risk for childhood food allergy

Abstract

Objective: To summarize recent data on the association between gut microbiome composition and food allergy (FA) in early childhood and highlight potential host-microbiome interactions that reinforce or abrogate oral tolerance.

Data sources: PubMed search of English-language articles related to FA, other atopic disease, and the gut microbiome in pregnancy and early childhood.

Study selections: Human studies published after 2015 assessing the relationship between the gut bacteriome and virome in the first 2 years of life and FA or food sensitization development in early childhood were prioritized. Additional human studies conducted on the prenatal gut microbiome or other atopic diseases and preclinical studies are also discussed.

Results: Children who developed FA harbored lower abundances of Bifidobacterium and Clostridia species and had a less mature microbiome during infancy. The early bacterial microbiome protects against FA through production of anti-inflammatory metabolites and induction of T regulatory cells and may also affect FA risk through a role in trained immunity. Infant enteric phage communities are related to childhood asthma development, though no data are available for FA. Maternal gut microbiome during pregnancy is associated with childhood FA risk, potentially through transplacental delivery of maternal bacterial metabolites, though human studies are lacking.

Conclusion: The maternal and infant microbiomes throughout the first 1000 days of life influence FA risk through a number of proposed mechanisms. Further large, longitudinal cohort studies using taxonomic, functional, and metabolomic analysis of the bacterial and viral microbiomes are needed to provide further insight on the host-microbe interactions underlying FA pathogenesis in childhood.

Figure 1.. Host-microbe interactions in food allergy.

Clostridia species produce SCFA and other metabolites that induce Treg differentiation, leading to production of TGF-β and IgA production and inhibition of Th2 differentation. Bacteria, such as Clostridia, produce SCFA that aid in maintenance of the intestinal epithelial barrier through upregulation of tight junction proteins. Through metabolism of aromatic amino acids, Bifidobacterium species, in particular B. infantis, upregulate galectin-1 in T cells, thereby preventing Th2 and Th17 cytokine response in favor of Treg and Th1. Lastly, phenotype of innate immune cells can change in response to an initial exposure via epigentic re-programming, eliciting a subsequent differential immune response upon re-exposure and activation by the original exposure. Created with BioRender.com.

Figure 2.. Potential mechanisms by which maternal prenatal SCFA protect against food allergy in childhood.

During pregnancy mothers eat dietary fiber (1), which is metabolized by gut bacteria to acetate (2). The acetate can be transplacentally delivered to the fetus (3) whereby the acetate, through histone deacetylase inhibition, will promote acetylation and increased expression of FOXP3, AIDCA, and PRDM1 (4). Increased expression of these genes will lead to increased T regulatory (Treg) cell differentiation and IgA production postnatally by the infant and thus protection against food allergy (FA). Created with BioRender.com.