Diet, Microbiota and Epigenetics as target for innovative strategies against food allergy: deciphering the protective mechanism of butyrate as crucial human milk effector

Objectives and study: The dramatic increase in food allergy prevalence and severity globally requires effective strategies. Food allergy derives from a defect in immune tolerance mechanisms. Immune tolerance is modulated by gut microbiota function and structure , and alterations in the gut microbiome composition (dysbiosis) early in the life have a pivotal role in the development of food allergy. Many environmental factors, including a low-fibre/high-fat diet, caesarean delivery, antiseptic agents, lack of breastfeeding, and drugs can induce gut microbiome dysbiosis, and have been associated with food allergy. New technologies and experimental tools have provided information regarding the importance of metabolites generated from dietary nutrients and selected probiotic strains that could act on immune tolerance mechanisms. The mechanisms are multiple and still not completely defined. Increasing evidence has provided useful information on optimal bacterial species/strains, dosage and timing for intervention. The increased knowledge of the crucial role played by nutrients and gut microbiota-derived metabolites is opening the way to a post-biotic approach in the stimulation of immune tolerance through epigenetic regulation. The mechanisms of the preventive effect of breast milk (BM) against food allergy (FA) are still largely undefined. The short chain fatty acid butyrate has a pivotal role in immune tolerance. We aimed to see whether BM butyrate concentrations are able to exert immune and non-immune tolerogenic effects in human enterocytes, peripheral blood mononuclear cells (PBMCs) from children affected by FA, and in FA animal model. Methods: Mature BM butyrate concentrations from 98 healthy women (aged 21-42 yrs) were assessed by gas-chromatography. Dose-dependent effects of butyrate in human enterocytes (Caco-2 cells) on immune (beta-defensin-3, HBD-3) and non-immune (mucus production; mucin 2, MUC2; tight-junction proteins, zonulin and occludin) were analyzed. PBMCs from 6 children with challenge-proven FA (2 ...