Scientific Study

Background: Rising rates of peanut allergy motivate investigations of its development to inform prevention and therapy. Microbiota and the metabolites they produce shape food allergy risk. Objective: To gain insight into gut microbiome and metabolome dynamics in the development of peanut allergy. Methods: We performed a longitudinal, integrative study of the gut microbiome and metabolome of infants with allergy risk factors but no peanut allergy from a multi-center cohort who were followed through mid-childhood. We performed 16S rRNA sequencing, short chain fatty acid measurements, and global metabolome profiling of fecal samples at infancy and at mid-childhood. Results: In this longitudinal, multi-center sample (n=122), 28.7% of infants developed peanut allergy by mid-childhood (mean age 9 years). Lower infant gut microbiome diversity was associated with peanut allergy development (P=0.014). Temporal changes in the relative abundance of specific microbiota and gut metabolite levels significantly differed in children who developed peanut allergy. Peanut allergy-bound children had different abundance trajectories of Clostridium sensu stricto 1 sp. (false discovery rate (FDR)=0.015) and Bifidobacterium sp. (FDR=0.033), with butyrate (FDR=0.045) and isovalerate (FDR=0.036) decreasing over time. Metabolites associated with peanut allergy development clustered within the histidine metabolism pathway. Positive correlations between microbiota, butyrate, and isovalerate and negative correlations with histamine marked the peanut allergy-free network. Conclusion: The temporal dynamics of the gut microbiome and metabolome in early childhood are distinct for children who develop peanut allergy. These findings inform our thinking on the mechanisms underlying and strategies for potentially preventing peanut allergy. https://doi.org/10.1016/j.jaci.2023.08.012