Gut Microbiome as Target for Innovative Strategies Against Food Allergy

Roberto Berni Canani, Lorella Paparo, Rita Nocerino, Carmen Di Scala, Giusy Della Gatta, Ylenia Maddalena, Aniello Buono, Cristina Bruno, Luana Voto, Danilo Ercolini, Roberto Berni Canani, Lorella Paparo, Rita Nocerino, Carmen Di Scala, Giusy Della Gatta, Ylenia Maddalena, Aniello Buono, Cristina Bruno, Luana Voto, Danilo Ercolini

Abstract

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 microbiome alterations (dysbiosis) have a pivotal role in the development of food allergy. Environmental factors, including a low-fiber/high-fat diet, cesarean delivery, antiseptic agents, lack of breastfeeding, and drugs can induce gut microbiome dysbiosis, and have been associated with food allergy. New experimental tools and technologies have provided information regarding the role 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. This review focused on the potential role of gut microbiome as the target for innovative strategies against food allergy.

Keywords: butyrate; dysbiosis; gut microbiota; gut microbiota metabolites; immune tolerance; mediterranean diet; probiotics; short chain fatty acids.

Figures

Figure 1
Figure 1
Gut microbiome as a target of intervention against food allergy. Several genetic, environmental, and dietary factors could modulate the gut microbiome-immune system axis influencing the occurrence of FA. For instance, increased family size, exposure to pets and/or rural environment, healthy diet (full of fibers, fermented foods, antioxidants, omega-3), breastfeeding and use of probiotics are associated with protection to FA. Conversely, C-section, prenatal, and early-life exposure to antibiotics/gastric acidity inhibitors/antiseptic agents, unhealthy diet (low fibers/high saturated fats and junk foods) may increase the risk for the development of FA. All these environmental factors act mainly on a modulation of gut microbiota structure and function which in turn could be responsible for the epigenetic regulation of genes involved in immune tolerance.
Figure 2
Figure 2
The Food Allergy pyramid. Children with FA present an increased risk to develop other conditions such as allergic disorders (atopic march), inflammatory bowel diseases (IBD), functional gastrointestinal disorders (FGIDs), and neuropsychiatric disorders. Several genetic factors are implicated in the pathogenesis of these conditions, but recent evidence suggest the pivotal role of gut microbiome dysbiosis (induced by environmental factors). Emerging evidence support the hypothesis of dysbiosis as the first hit in the development of alterations in intestinal barrier and immune system function (responsible for the occurrence of FA and atopic march) and dysregulation of the brain-gut endocrine-immune system axis (responsible for the occurrence of FGIDs, IBD, and neuropsychiatric disorders), at least in part through an activation of epigenetic mechanisms.
Figure 3
Figure 3
The structure of the gut microbiome-immune system axis. Within the gut microbiome-immune system axis the cross talk between microbes and the immune system may occur directly through microbial components or indirectly through the action of metabolites, such as SCFAs. A positive modulation of this axis can counteract the pathogenesis of FA by promoting epithelial integrity, gut permeability, mucus production, CD103+ tolerogenic DCs, Treg differentiation, cytokines production, and sIgA release from plasma cells.
Figure 4
Figure 4
Toward a gut microbiome-based precision medicine against food allergy. We are approaching an era where the metagenomic and metabolomic evaluation of gut microbiota in children at risk for FA will drive personalized intervention to preserve or restore an “eubiosis” state based on nutritional counseling and educational programs.

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