Longitudinal disease-associated gut microbiome differences in infants with early food allergic manifestations
Abstract Complex interactions between the gut microbiome and immune cells in infancy are thought to be part of the pathogenesis for the marked rise in pediatric allergic diseases, particularly food allergies. Food protein-induced allergic proctocolitis (FPIAP) is commonly the earliest recognized non-IgE-mediated food allergy in infancy and is associated with atopic dermatitis and subsequent IgE-mediated food allergy later in childhood. Yet, a large prospective longitudinal study of the microbiome of infants with FPIAP (including samples prior to symptom onset) has not been done. Here we analyzed 954 longitudinal samples from 160 infants in a nested case-control study (81 who developed FPIAP, and 79 matched controls) from 1 week to 1 year of age by 16S rRNA ribosomal gene sequencing as part of the Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) Study. We confirmed that vaginally delivered infants had a greater abundance of Bacteroides, infants who received any breast milk had a greater abundance of Bifidobacterium, and that overall bacterial richness rose over the first year. We found key differences in the microbiome of infants with FPIAP, most strongly a higher abundance of a genus of Enterobacteriaceae and a lower abundance of a family of Clostridiales during the symptomatic period, as well as other key taxonomic differences across symptom states including prior to symptom onset. This study contributes to the larger body of literature examining structural development of the early life gut microbiome and provides a foundation for more mechanistic investigation into the pathogenesis and microbial effects on FPIAP and subsequent food allergic diseases in childhood.