Butyrate as a bioactive human milk protective component against food allergy

Abstract

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-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.

Milk Fatty Acid Profiles in Different Animal Species: Focus on the Potential Effect of Selected PUFAs on Metabolism and Brain Functions

“…Indeed, human milk fat is high in unsaturated fatty acids and PUFAs, particularly the essential fatty acids LA and ALA. The beneficial effects of human milk also depend on its bioactive/immunomodulatory factors (oligosaccharides, lactose, glycosaminoglycans) [ 61 ]. The World Health Organization recommends the exclusive breastfeeding of infants for the first 6 months of age, since maternal milk reduces the incidence of neonatal necrotizing enterocolitis, gastroenteritis, respiratory infection, and immunologically based disease, and improves later cognitive development [ 62 , 63 ].…”

Butyrate: A Link between Early Life Nutrition and Gut Microbiome in the Development of Food Allergy

“…Interestingly, butyrate is the only SCFA produced exclusively by microbial gut fermentation, while other SCFAs are affected by host metabolism [10]. Recent findings support the hypothesis that butyrate might contribute to the development of immune oral tolerance and in the prevention and treatment of food allergies [11][12][13]. This review summarizes what is currently known about the role of butyrate in food allergies, underlining the complex interplay among early life nutrition, gut microbiome, and immune system.…”

“…In peripheral blood mononuclear cells (PBMCs) from children with food allergy, butyrate enhanced IL-10, IFN-γ, and Forkhead box P3 (FOXP3) expression through epigenetic mechanisms. Moreover, it promoted dendritic cells, regulatory T cells (Tregs), and the precursors of M2 macrophages [11]. The authors concluded that an effective concentration of butyrate in human milk could contribute to explain the protective role of breastfeeding against food allergy.…”

“…In a mouse model, butyrate has been shown to upregulate the expression of several biomarkers of gut barrier integrity as well as tolerogenic cytokines. In animal models of food allergy, pre-treatment with butyrate significantly reduced allergic responses because of an upregulated expression of tolerogenic cytokines, an inhibition of Th2 cytokine production, and a modulation of oxidative stress [11]. In human enterocytes, butyrate has been shown to stimulate mucin production, tight junctions, and human beta defensin-3 expression.…”

“…Human milk is a complex biological system and many bioactive factors present in human milk can affect infant immune system maturation [55]. A recent study by Paparo et al [11] suggests the importance of butyrate as a bioactive human milk component that can protect against the onset of food allergies. Human milk contains a significant level of butyrate.…”