Butyrate as a Bioactive Human Milk Protective Component Against Food Allergy

Abstract

To understand the concentration of butyrate, a short chain fatty acid and metabolite derived from gut microbiota, in human milk and the mechanisms of immune tolerance.A total of 109 healthy mothers (aged 21–42 years) were enrolled after term singleton pregnancy in Italy.By using gas chromatography-mass spectrometry, the concentration of human milk butyrate was measured. By using in vivo and in vitro models, the tolerogenic mechanisms of human milk butyrate were evaluated.The median butyrate concentration of 0.75 mM was responsible for the maximum modulatory effects observed. In the mouse model, upregulation of several biomarkers important for gut barrier integrity by butyrate was seen. In animal models of food allergy, pretreatment with butyrate significantly reduced allergic response with inhibition of T helper 2 cytokine production and stimulation of tolerogenic cytokines. In human cell models, stimulation of human β defensin-3 and tight junctions’ expression in human enterocytes by butyrate were seen in peripheral blood mononuclear cells from children with food allergy; expression of interleukin 10, interferon γ and forkhead box P3 through epigenetic mechanisms occurred. Precursors of regulatory T cells and dendritic cells were promoted.Butyrate may have a pivotal role in protection against food allergy.Food allergy is a pervasive problem throughout the world. Breastfeeding is considered to have a protective effect against the development of food allergy, although previous data have revealed conflicting rates of efficacy. The underlying mechanism for food allergy protection has also been unclear. The immunoregulatory effectiveness of human milk may be secondary to butyrate concentration, as seen in this study. The variation of butyrate concentration in individual’s human milk may explain the inconsistent evidence for human milk’s protection against food allergy from previous studies. Butyrate supplementation to infants or lactating mothers is a potential strategy to prevent the development of food allergy.