The oral environment in food allergy development (oneida)

Cooperative Agreement Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded Icahn School of Medicine at Mount Sinai a Cooperative Agreement valued at $6.73 million under the Allergy and Infectious Diseases Research program (CFDA 93.855) for the period August 1, 2025 through June 30, 2029. This award supports "The Oral Environment in Food Allergy Development (ONEIDA)" project, which aims to characterize the early-life trajectory of the oral environment during food allergy development in children. The research leverages longitudinal samples and existing data from the NIH/NIAID Systems Biology of Early Atopy (SUNBEAM) study, a multi-center birth cohort of 2,500 children across the United States with extensive longitudinal phenotyping, including doctor-supervised food challenges for food allergy assessment.

The principal deliverables under this cooperative agreement include comprehensive characterization of oral mucosal immunology, oral microbial communities, metabolites, and their cross-talk with systemic factors during the first three years of life in children who develop food allergy. Specifically, the research will examine differences in food-specific antibody levels in saliva between food-allergic children and those who are sensitized but non-allergic, and analyze how allergen-specific antibody profiles correlate with food allergy thresholds, severity, and organ-specific symptoms. Additionally, the project will investigate variations in the saliva microbiome and metabolome associated with food allergy development, generating scientific evidence to advance understanding of food allergy origins and potentially informing prevention and therapeutic strategies.

Abstract

Food allergy, an incurable condition affecting ~10% of the US population, is a departure from immune homeostasis where aberrant antibody response, microbial dysbiosis, and local and systemic symptoms are well-reported. With exposure to culprit foods, individuals with food allergy experience symptoms including oral swelling, hives, vomiting, and anaphylaxis. The oral mucosa is the first interface between ingested food antigens and the immune system. Our studies have revealed differences in food-specific antibody levels in saliva between food allergic children and those who are only food sensitized. We have shown that allergen- specific antibody profiles in saliva can predict food allergy threshold, severity, and organ-specific symptoms. We have also found that the saliva microbiome and metabolome differ in children with and without food allergy. Building on this work, we aim to study the origins of food allergy and propose to characterize the early-life trajectory of the oral environment as food allergy arises. To date, there has been no study of the oral environment as children acquire food allergy. Our central hypothesis is that the development of food allergy is associated with distinct trajectories during the first three years of life in oral mucosal immunology, oral microbial communities and metabolites, and their cross-talk with systemic factors. We will leverage longitudinal samples and existing data from the NIH/niaid systems biology of early atopy (sunbeam) study, a multi-center birth cohort of 2,500 children from across the US who have undergone extensive longitudinal phenotyping, including doctor-supervised food challenges for food allergy assessment. We have been leading and working on sunbeam since IT began. To address our first hypothesis that the inception of food allergy is associated with a distinct oral mucosal immunologic trajectory, we will characterize the development of allergen-specific antibodies and cytokine milieu in saliva during the first 3 years of life and identify saliva antibody and cytokine predictors of food allergy inception (aim 1). To address our second hypothesis that children who attain food allergy host different oral microbial communities and metabolites, we will profile the saliva microbiome and metabolome during the first 3 years of life and chart microbial and metabolite dynamics associated with food allergy acquisition (aim 2). Our third hypothesis is that directional cross-talk between the oral and systemic environments is associated with food allergy development. We will build temporal networks and employ causal methods to integrate the multi-dimensional oral data generated by this study with multi-omic systemic data that we have in hand for the same participants to identify directional relationships between the oral and systemic environments over time and their causal impact on food allergy onset (aim 3). This study will generate unprecedented findings on the immunologic, microbial, and metabolomic trajectories of the early-life oral environment and their relationship with food allergy development. Findings could inform food allergy prevention and biomarkers using non-invasive saliva samples.