Background: 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-immunoglobulin E (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. Results: 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 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. We saw some of these significant taxonomic differences even prior to symptom onset. There were no consistent longitudinal differences in richness or stability diversity metrics between infants with FPIAP and healthy controls. Conclusions: This study is the first to identify differences in the infant gut microbiome in children who develop FPIAP, some even before they develop symptoms, and provides a foundation for more mechanistic investigation into the pathogenesis of FPIAP and subsequent food allergic diseases in childhood. [MediaObject not available: see fulltext.].
Bibliographical noteFunding Information:
We thank Tiffany Poon and Luke Besse for project management, Dr. Michael Elkort and Dr. Susan Reuter along with the full staff at Pediatrics at Newton Wellesley for patient enrollment and sample collection, GMAP participants and their families, and the Broad Institute Microbial “Omics Core and Genomics Platform” for sample processing and 16S rRNA gene sequencing data generation.
The GMAP cohort was supported by the Gerber Foundation (1685–3680), the Demarest Lloyd Jr Foundation (230465), and the Food Allergy Science Initiative (229711). VMM and YVV were supported by grants from the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (1K23AI151555-01A1 and K23AI130408, respectively). MY is the Rosalind, Paul and Robin Berlin Faculty Development Chair in Perinatal Research, was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (1K99DK11322401) and the Azrieli Foundation.
© 2022, The Author(s).