Immune components of early breastmilk and allergy risk in children from the EDEN and Elfe birth cohort

The role of breastfeeding in the prevention of allergies in childhood is still controversial and biological mechanisms are unclear. Within non-nutritional bioactive components of breastmilk (BM), immunomodulatory components and their effects on child allergy are still poorly investigated. We aimed to study the associations between immune and growth factor concentrations in early BM and risk of allergy in childhood. The study was conducted on a random sample of 247 and 359 mother-child dyads from the EDEN and Elfe birth cohorts, respectively. About 50 cytokines, antibodies and growth factors from early BM were analyzed using multiplexed kits (Berdi et al., 2018). Allergic and respiratory multimorbidity clusters up to 8 years (EDEN) and 5 years (Elfe) were previously identified (Delvert et al., 2023): “asymptomatic”, “asthma only”, “allergies without asthma”, “multi-allergic”, with an additional cluster exclusively in Elfe, “Early wheezers without asthma”. The associations between multimorbidity clusters and each immune factor concentration were assessed using multinomial logistic regression models in each subcohort separately with “asymptomatic” cluster as reference group, adjusted for time of BM collection. While different immune factors were negatively associated with multimorbidity clusters in each subcohort, two of them were associated in both; in EDEN, IL-17A and RANTES (from IL-8 family) were negatively associated with “allergies without asthma” (OR [95% CI] = 0.39 [0.16; 0.91] for 1 SD increase) and “multi-allergic” (OR = 0.45 [0.24; 0.86] for 1 SD increase) clusters respectively. Similarly, in Elfe, IL-17A and RANTES were negatively associated with “allergies without asthma” (OR = 0.47 [0.25; 0.88] for 1 SD increase) and “multi-allergic” (OR (3rd vs. 1st tertile) = 0.36 [0.15; 0.86]) clusters, respectively. Our study evidenced associations between immune components in BM and allergy in childhood, with notably a robust and negative association for RANTES and IL-17A. Our results argue for the major role of bioactive BM components in the establishment of immune (intestinal) homeostasis in neonate, protecting from later immune disorders.