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Wise et al.

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cytokine release (such as IL 4, IL-13, and IFN- γ ) induces further “leakiness” of the apical junctional complex via various mechanisms, allowing increased levels of allergen penetration. 367 Evidence suggests that this barrier impairment may be reversed with corticosteroids. Fluticasone propionate has been found to increase expression of tight junction proteins zonula occludens 1 and occludin and a more intact nasal epithelial barrier. 322 Corticosteroids have not, however, been shown to cause thinning of nasal epithelium. 322,431 Allergy is now considered both a systemic and local epithelial condition. 337 Evidence points to the epithelium being an active participant in the development and progress of allergy, rather than as a passive barrier. 432 Birch pollen has been found to rapidly bind to Bet v 1– binding proteins in sensitized nasal epithelium, and is transported through a lipid raft and caveolar-dependent process before binding to mast cells in the lamina propria. 433-435 Epithelial response to allergens differs from healthy individuals in that allergic patients do not mount as robust an epithelial defense response to allergens, leading to increased penetration of allergens. 432 The human microbiome comprises the complex community of microorganisms that resides in and interacts with the human body. The adult intestine is a haven to approximately 100 trillion microbes and it is thought that the microbiome accounts for roughly 90% of all the cells in the human body. 436,437 The microbiomes of individuals vary, likely due to the fact that the growth, development, and composition of the microbiome are affected by intricate interactions between the environment, diet, and host-related factors. 437 With the advent of culture-independent high-throughput bacterial DNA sequencing techniques, a detailed description of the composition and variety of the microbiome can be described among organs and individuals. 438 The Human Microbiome Project began in 2007, and as a result, extensive data have emerged examining the associations of the microbiota of the respiratory tract, oral cavity, gut, skin, and genitourinary tract to the development of disease processes including allergy and asthma. 437 Increasing literature in animals and humans has implicated changes in the microbiome with the development of allergic disease. 439,440 Mechanistically, a disruption in gastrointestinal bacteria is thought to alter mucosal immunological tolerance. 441 Several authors have found associations of reduced gut microbial diversity with development of allergic disease in school-aged children. 442,443 For example, the development of allergic symptoms in children has been associated with overall lower microbial diversity, increased prevalence of Bacteroides and Bifidobacterium adolescentis , and lower counts of Akkermansia muciniphilia , Faecalibacterium prausnitzii , and Clostridium . 444 In addition, Fujimura et al. 445 recently noted that a lower abundance of Bifidobacterium , Akkermansia , and Faecalibacterium were associated with a higher risk of development of polysensitization by age 2 years and physician-diagnosed asthma by age 4 years. The authors concluded that neonatal intestinal microbial dysbiosis may foster CD4+ T-cell dysfunction associated with childhood allergic disease. 445,446

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IV.G. Microbiome

Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.