1. Butyrate as a bioactive human milk protective component against food allergy
- Author
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Lorella Paparo, F. Messina, Annalisa Agangi, Francesco Montella, Cristina Bruno, Marcello Napolitano, Annibale Puca, Antonio Amoroso, Giusy Della Gatta, Rita Nocerino, Giovanna Trinchese, Laura Pisapia, Annalisa Passariello, Roberto Berni Canani, Maria Pina Mollica, Elena Ciaglia, Carmen Di Scala, Carmen De Caro, Roberto Russo, Luana Voto, Antonio Calignano, Margherita Di Costanzo, Rosita Aitoro, Paparo, L., Nocerino, R., Ciaglia, E., Di Scala, C., De Caro, C., Russo, R., Trinchese, G., Aitoro, R., Amoroso, A., Bruno, C., Di Costanzo, M., Passariello, A., Messina, F., Agangi, A., Napolitano, M., Voto, L., Gatta, G. D., Pisapia, L., Montella, F., Mollica, M. P., Calignano, A., Puca, A., and Berni Canani, R.
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immune tolerance ,short‐chain fatty acids ,short-chain fatty acids ,Immunology ,Stimulation ,Butyrate ,Pharmacology ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Immune tolerance ,In vivo ,medicine ,Animals ,Immunology and Allergy ,tolerogenic mechanism ,Milk, Human ,Chemistry ,breast milk ,In vitro ,Gastrointestinal Microbiome ,Butyrates ,Allergic response ,Original Article ,Basic and Translational Allergy Immunology ,ORIGINAL ARTICLES ,short-chain fatty acid ,Food Hypersensitivity ,Oxidative stress - 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., Human milk contains a significant level of the short‐chain fatty acid butyrate. At concentration detectable in human milk, butyrate effectively modulates several tolerogenic mechanisms involved in the protection against food allergy. The protective role of human milk against food allergy could be related, at least in part, to the presence of an effective concentration of butyrate
- Published
- 2020
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