<h3>Introduction</h3> The pathophysiology of IgE mediated food reactions (FR) is multifactorial. This multi-omic analyses utilized host and microbial factors to better understand the immunological origins of FR's. <h3>Methods</h3> This longitudinal cohort study included 129 term infants, identified as FR (n=27) or non-FR (n=92) using the Infant Feeding Practices-II survey (confirmed with medical records). Saliva was collected at 6 months for multi-omic analysis of cytokines, mRNA, microRNAs, and the microbiome. <h3>Results</h3> None of the salivary cytokines (CXCL10, IL-8, IL-6, IL-18) displayed differences between groups. However, the Th1/Th2 ratio (IL-8/IL-6) was nominally higher (d = 0.56, p = 0.043, FDR = 0.30) among infants with a food reaction. One mRNA (STAT6, p = 0.039, FDR = 0.17, d = 0.045), two miRNAs (let-7e-5p, p = 0.031, FDR = 0.12, d = 0.51; miR-151a-5p, p = 0.041, FDR = 0.13, d = 0.52), and one bacterial phylum (Cyanobacteria, p = 0.024, FDR = 0.19, d = 0.72) displayed nominal differences between 27 infants with food reactions (FR) and 92 peers with no food reactions (NFR). All four omics features were higher in infants with FR. A logistic regression model employing maternal/infant traits and environmental exposures and four multi-omic features (IL-8/IL-6, miR-151a-5p, STAT6, Cyanobacteria) accounted for an additional 31% of the variance between groups (p = 0.15, AUC = 0.83, sensitivity = 97%, specificity = 48%). <h3>Conclusion</h3> Multi-omic analysis of saliva may enhance understanding of key biological factors that contribute towards developing immune mediated food reactions.