Impact of Infant Formula on Resolution of Cow's Milk Allergy

Cow's Milk Allergy (CMA) is prevalent and most often presents during infancy. Disease manifestations vary through a range of immediate and delayed inflammatory responses to milk protein from anaphylaxis to enterocolitis. The natural history is also highly variable; most children will achieve clinical tolerance early in life, while a minority will have disease persisting to adulthood for reasons that are not known. Most presentations are mild and are managed by restriction or reduction of immunologically intact milk protein with reintroduction sometime after a year of age; however, there are data to suggest that some level of antigenic stimulation may be beneficial. Furthermore, recent data suggest that oral probiotic exposure may also promote tolerance, though the kinetics of tolerance acquisition, the interaction between these two factors (probiotics and milk antigen exposure) and their relationship to regulatory T cell responses are all poorly defined. Therefore, there is an unmet need to identify dietary interventions, along with corresponding immune responses, that favor the promotion of tolerance. A major objective will be to measure the effect probiotics have on the development of tolerance to milk antigen over time. By following these infants during the first year of life, and repeatedly collecting blood and stool samples from them, we will be poised to analyze their stool microbiome signatures, and we will estimate the frequency, phenotype and TCR diversity of milk-specific T cells over time. By repeatedly challenging them with more immunologically intact milk protein, we will better define the kinetics of CMA resolution and its association to these variables. This information is likely to further elucidate CMA disease mechanisms and identify possible biomarkers of disease resolution versus persistence. It will be directly useful for evaluating the efficacy of probiotics and hydrolyzed formula for promoting milk tolerance.