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Environmental factors and eosinophilic esophagitis.

ABSTRACT: The incidence and prevalence of eosinophilic esophagitis (EoE) have markedly increased over the past 2 decades, outpacing increased detection of the disease. Although genetic susceptibility markers for EoE have begun to be elucidated, the rate at which EoE has increased in incidence suggests environmental factors predominate. Despite many advances in understanding of the pathogenesis of EoE, the cause of EoE is unknown. This article reviews the emerging data related to environmental risk factors for EoE. Many of these environmental factors are rooted in the theoretical framework of the hygiene hypothesis, specifically mediation of disease development through dysbiosis. Other hypotheses are based on associations that have been observed in studies of non-EoE allergic disease. We describe the evidence that early-life exposures, including antibiotic use, acid suppression, and cesarean delivery, can increase the risk of disease. We also describe the evidence that infectious agents, such as Helicobacter pylori, are inversely associated with disease. Current evidence on geographic risk factors, such as population density, climate zone, and seasonality, is reviewed. We also describe behavioral factors that have been evaluated. Limitations of the existing research are discussed, and recommendations for future areas of research, including assessment of gene-environment interaction, are presented.

SUBMITTER: Jensen ET

PROVIDER: S-EPMC6035771 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Environmental factors and eosinophilic esophagitis.

Jensen Elizabeth T ET Dellon Evan S ES

The Journal of allergy and clinical immunology 20180502 1

The incidence and prevalence of eosinophilic esophagitis (EoE) have markedly increased over the past 2 decades, outpacing increased detection of the disease. Although genetic susceptibility markers for EoE have begun to be elucidated, the rate at which EoE has increased in incidence suggests environmental factors predominate. Despite many advances in understanding of the pathogenesis of EoE, the cause of EoE is unknown. This article reviews the emerging data related to environmental risk factors ...[more]

PMID: 29729305

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Project description:Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory disease of the esophagus characterized predominantly by eosinophilic inflammation, leading to esophageal dysfunction. Converging data have placed the esophageal epithelium at the center of disease pathogenesis. In particular, the main EoE disease susceptibility loci at 2p23 and 5p22 encode for gene products that are produced by the esophageal epithelium: the intracellular protease calpain 14 and thymic stromal lymphopoietin, respectively. Furthermore, genetic and functional data establish a primary role for impaired epithelial barrier function in disease susceptibility and pathoetiology. Additionally, the EoE transcriptome, a set of genes dysregulated in the esophagi of patients with EoE, is enriched in genes that encode for proteins involved in esophageal epithelial cell differentiation. This transcriptome has a high proportion of esophagus-specific epithelial genes that are notable for the unexpected enrichment in genes encoding for proteases and protease inhibitors, as well as in IL-1 family genes, demonstrating a previously unappreciated role for innate immunity responses in the esophagus under homeostatic conditions. Among these pathways, basal production of the serine protease inhibitor, Kazal-type 7 (SPINK7) has been demonstrated to be part of the normal differentiation program of esophageal epithelium. Profound lost expression of SPINK7 occurs in patients with EoE and is sufficient for unleashing increased proteolytic activity (including urokinase plasminogen activator), impaired barrier function, and production of large quantities of proinflammatory and proallergic cytokines, including thymic stromal lymphopoietin. Collectively, we put forth a model in which the esophagus is normally equipped as an anti-inflammatory sensing organ and that defects in this pathway, mediated by epithelial protease/protease inhibitor imbalances, unleash inflammatory responses resulting in disorders, such as EoE.

Dataset Information

Environmental factors and eosinophilic esophagitis.

Publications

Environmental factors and eosinophilic esophagitis.

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