A prospective microbiome-wide association study of food sensitization and food allergy in early childhood

Background: Alterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development. Methods: Intestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high-dose vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 with evidence of IgE sensitization. Analysis was performed using Phyloseq and DESeq2; P-values were adjusted for multiple comparisons. Results: Complete data were available for 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases and controls. The genera Haemophilus (log₂ fold change −2.15, P=.003), Dialister (log₂ fold change −2.22, P=.009), Dorea (log₂ fold change −1.65, P=.02), and Clostridium (log₂ fold change −1.47, P=.002) were underrepresented among subjects with food sensitization. The genera Citrobacter (log₂ fold change −3.41, P=.03), Oscillospira (log₂ fold change −2.80, P=.03), Lactococcus (log₂ fold change −3.19, P=.05), and Dorea (log₂ fold change −3.00, P=.05) were underrepresented among subjects with food allergy. Conclusions: The temporal association between bacterial colonization and food sensitization and allergy suggests that the microbiome may have a causal role in the development of food allergy. Our findings have therapeutic implications for the prevention and treatment of food allergy.