Dataset Information

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.

SUBMITTER: Paparo L

PROVIDER: S-EPMC8247419 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundImmune features of infants with food allergy have not been delineated.ObjectivesWe sought to explore the basic mechanisms responsible for food allergy and identify biomarkers, such as skin prick test (SPT) responses, food-specific IgE levels, and mononuclear cell responses, in a cohort of infants with likely milk/egg allergy at increased risk of peanut allergy.MethodsInfants aged 3 to 15 months were enrolled with a positive SPT response to milk or egg and either a corresponding convincing clinical history of allergy to milk or egg or moderate-to-severe atopic dermatitis. Infants with known peanut allergy were excluded.ResultsOverall, 512 infants (67% male) were studied, with 308 (60%) having a history of a clinical reaction. Skin test responses, detectable food-specific IgE, or both revealed sensitization as follows: milk, 78%; egg, 89%; and peanut, 69%. SPT responses and food-specific IgE levels were discrepant for peanut (15% for IgE > or = 0.35 kU(A)/L and negative SPT response vs 8% for positive SPT response and IgE <0.35 kU(A)/L, P = .001). Mononuclear cell allergen stimulation screening for CD25, cytokine-inducible SH2-containing protein (CISH), forkhead box protein 3 (FOXP3), GATA3, IL10, IL4, IFNG, and T-box transcription factor (TBET) expression by using casein, egg white, and peanut revealed that only allergen-induced IL4 expression was significantly increased in those with clinical allergy to milk (compared with nonallergic subjects) and in those sensitized to peanut, despite the absence of an increase in GATA3 mRNA expression.ConclusionsInfants with likely milk/egg allergy are at considerably high risk of having increased peanut-specific IgE levels (potential allergy). Peanut-specific serum IgE levels were a more sensitive indicator of sensitization than SPT responses. Allergen-specific IL4 expression might be a marker of allergic risk. Absence of an increase in GATA3 mRNA expression suggests that allergen-specific IL-4 might not be of T-cell origin.