Butyrate as bioactive human milk protective component against food allergy.

BACKGROUND Food allergy (FA) is a growing health problem worldwide. Effective strategies are advocated to limit the disease burden. Human milk (HM) is considered a protective factor for FA, but its mechanisms remain unclear. Butyrate is a gut microbiota-derived metabolite able to exert several immunomodulatory functions. OBJECTIVES To define the butyrate concentration in HM. To see whether the butyrate concentration detected in HM is able to modulate the mechanisms of immune tolerance. METHODS HM butyrate concentration from 109 healthy women was assessed by GS-MS. The effect of HM butyrate on tolerogenic mechanisms was assessed in vivo and in vitro models. RESULTS The median butyrate concentration in mature HM was 0.75 mM. This butyrate concentration was responsible for the maximum modulatory effects observed in all experimental models evaluated in this study. Data from mouse model show that in basal condition, butyrate up-regulated the expression of several biomarkers of gut barrier integrity, and of tolerogenic cytokines. Pre-treatment with butyrate significantly reduced allergic response in three models of FA, with a stimulation of tolerogenic cytokines, inhibition of Th2 cytokines production and a modulation of oxidative stress. Data from human cells models show that butyrate stimulated human beta defensin-3, mucus components and tight junctions expression in human enterocytes, and IL-10, IFN-γ and FoxP3 expression through epigenetic mechanisms in PBMCs from FA children. Furthermore, it promoted the precursors of M2 macrophages, DCs and regulatory T cells. CONCLUSION The study's findings suggest the importance of butyrate as a pivotal HM compound able to protect against FA.