Butyrate as bioactive human milk protective component against food allergy

Lorella Paparo, Rita Nocerino, Elena Ciaglia, Carmen Di Scala, Carmen De Caro, Roberto Russo, Giovanna Trinchese, Rosita Aitoro, Antonio Amoroso, Cristina Bruno, Margherita Di Costanzo, Annalisa Passariello, Francesco Messina, Annalisa Agangi, Marcello Napolitano, Luana Voto, Giusy Della Gatta, Laura Pisapia, Francesco Montella, Maria Pina MollicaAntonio Calignano, Annibale Puca, Roberto Berni Canani

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalAllergy: European Journal of Allergy and Clinical Immunology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • breast milk
  • immune tolerance
  • short-chain fatty acids
  • tolerogenic mechanism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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