The Role of Gut Microbiota and Leaky Gut in the Pathogenesis of Food Allergy

Abstract

Food allergy (FA) is a growing public health concern, with an increasing prevalence in Western countries. Increasing evidence suggests that the balance of human gut microbiota and the integrity of our intestinal barrier may play roles in the development of FA. Environmental factors, including industrialization and consumption of highly processed food, can contribute to altering the gut microbiota and the intestinal barrier, increasing the susceptibility to allergic sensitization. Compositional and functional alterations to the gut microbiome have also been associated with FA. In addition, increased permeability of the gut barrier allows the translocation of allergenic molecules, triggering Th2 immune responses. Preclinical and clinical studies have highlighted the potential of probiotics, prebiotics, and postbiotics in the prevention and treatment of FA through enhancing gut barrier function and promoting the restoration of healthy gut microbiota. Finally, fecal microbiota transplantation (FMT) is now being explored as a promising therapeutic strategy to prevent FA in both experimental and clinical studies. In this review article, we aim to explore the complex interplay between intestinal permeability and gut microbiota in the development of FA, as well as depict potential therapeutic strategies.

Keywords: fecal microbiota transplantation; food allergy; gut microbiota; intestinal barrier; leaky gut; prebiotics; probiotics; synbiotics.

Figure 1

The role of gut microbiota and leaky gut in the pathogenesis of food allergy. Under physiological conditions, a eubiotic gut microbiota promotes the differentiation of T lymphocytes into T regulatory cells, leading to immune tolerance of the gut [96]. Conversely, in the context of a leaky gut barrier and intestinal dysbiosis, epithelial-derived cytokines such as thymic stromal lymphopoietin (TSLP), interleukin 33 (IL-33), and IL-25 are released in response to various gut barrier disruptors [97,98]. These alarmins promote a pro-allergic microenvironment by activating T helper 2 (Th2) and type 2 innate lymphoid cells (ILC2), resulting in the release of proinflammatory cytokines (e.g., IL-4, IL-5, and IL-13) [95]. Furthermore, dysbiotic gut microbiota induce the differentiation of Th2 cells, promoting the IgE class-switching process in B cells [100]. After sensitization to a specific food allergen, which is also favored by leaky gut, allergen-specific IgE antibodies become immobilized on the surface of basophils and mast cells. Upon subsequent exposure to the allergen, these cells release histamine and other proinflammatory mediators (e.g., leukotrienes and type 2 cytokines) [101,102], worsening gut permeability and amplifying type 2 inflammation [103]. Abbreviations: FcεRI, high-affinity IgE receptor; IL, interleukin; IgE, immunoglobulin E; ILC2, innate lymphoid cell2; Th0, naive T cell; Th2, helper T cell 2; T_reg, T regulatory cell; TLSP, thymic stromal lymphopoietin; sIgA, secretory IgA.