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) could be considered as a protective factor against FA, but its mechanisms remain unclear. Butyrate is a gut microbiota-derived metabolite able to exert several immunomodulatory functions. We aimed to define the butyrate concentration in HM, and 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 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. Pretreatment with butyrate significantly reduced allergic response in three animal models of FA, with a stimulation of tolerogenic cytokines, inhibition of Th2 cytokines production and a modulation of oxidative stress. Data from human cell models show that butyrate stimulated human beta defensin-3, mucus components and tight junctions expression in human enterocytes, and IL-10, IFN-gamma 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.

Automated summary

This study found that the concentration of butyrate in human milk has significant modulatory effects in various experimental models, reducing allergic responses and promoting the expression of tolerogenic cytokines. Butyrate also showed potential in human cell models for promoting the expression of key genes through epigenetic mechanisms. Overall, butyrate appears to play a pivotal role in protecting against food allergies.