Background: Immunomodulatory proteins in human milk (HM) can shape infant immune development. However, strategies to modulate their levels are currently unknown. This study investigated whether maternal prebiotic supplementation alters the levels of immunomodulatory proteins in HM. Methods: The study was nested within the SYMBA double-blind randomised controlled trial (ACTRN12615001075572), which is investigating the effects of maternal prebiotic (scGOS/lcFOS) supplementation from <21 weeks gestation during pregnancy until 6-months postnatal during lactation on child allergic disease risk. Mother-child dyads receiving prebiotics (n=46) or placebo (n=54) were included in this study. We measured the levels of 24 immunomodulatory proteins in HM collected at 2, 4 and 6 months. Results: Cluster analysis showed that the overall immunomodulatory protein composition of milk samples from both groups was similar. Prebiotic-supplemented women had decreased levels of TGF-β1 at 2 months, IgG1 at 4 months and sCD14 at 6 months (p=0.03, 0.03 and 0.04, respectively). IL-5 levels were increased in the prebiotic group compared to the control group at 4 and 6 months (p=0.02 and 0.04, respectively). After adjustment for multiple comparisons, the statistical differences between the prebiotic and placebo groups were no longer present (p>0.05). Conclusion: This study is the first to comprehensively trial scGOS/lcFOS intake during pregnancy and indicate potentially altered levels of immunomodulatory proteins in HM. Future research will elucidate the significance of change in milk content in immunomodulatory compounds in the prevention of allergy risk (and beyond), filling a major gap in dietary advice to pregnant and/or lactating women.

Immunoglobulin E (IgE)-mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. In genetically-predisposed subjects exposure to minute quantities of allergens leads to the production of IgE antibodies which is termed allergic sensitization and mainly occurs in early childhood. Allergen-specific IgE then binds to the high (FcRI) and low affinity receptors (FcRII, also called CD23) for IgE on effector cells and antigen-presenting cells, respectively. Subsequent and repeated allergen exposure increases allergen-specific IgE levels and, by receptor cross-linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE-facilitated allergen presentation perpetuates T cell-mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen-specific IgG and IgA antibodies usually recognize different epitopes on allergens compared to IgE, and do not efficiently interfere with allergen-induced inflammation. However IgG and IgA antibodies to these important IgE epitopes can be induced by allergen-specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti-IgE treatment does the same by preventing IgE from binding to its receptor on mastcells and basophils. Here we review the complex interplay of allergen-specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.