ReviewNature reviews. Immunology2021
Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?
Review in Nature reviews. Immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07271381 (THREAT), which is not on this map. Cited by 497 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
THREAT: Testing Harms Related to Exposure to Allergenic and Epithelial Toxins
Who cites it
497 citing papers in PubMed, 2 syntheses or guidelines pooled it, 888 citations in OpenAlex.
- Nutrition and Gut Microbiome in the Prevention of Food Allergy.Nutrients · 2025Pooled it
- The Role of Epithelial-Derived Extracellular Vesicles in Allergic Sensitisation: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Single-cell analysis of chromatin accessibility in the human intestine identifies regulatory programs and clarifies genetic associations in Crohn's disease.Nature genetics · 2026Article
- Pathways of Epithelial Barrier Breakdown and Remodeling in Esophageal Organoids by Commonly Used Surfactants.Allergy · 2026Article
- Allergic Diseases and Risk of Incident Autoimmune Diseases: Phenotype-Specific Patterns and Multimorbidity Effects in a Nationwide Cohort.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Article
- Article
- Failed Mucosal Allostasis Distinguishes Murine IgG- From IgE-Mediated Recurrent Severe Anaphylaxis.Allergy · 2026Article
- Common Food Emulsifiers Impair Epithelial Barrier Integrity and Trigger Pro-Inflammatory Responses and IgE Production.Allergy · 2026Article
- Diet-Microbiome-Immune Interactions at the Gut Mucosa in Food Allergy: Mechanisms, Gaps, and Therapeutic Implications.Allergy · 2026Review
- Detergent-Containing Toothpaste Decreases Esophageal Mucosal Impedance and Alters Salivary Properties in Humans.Allergy · 2026Article
- Leptin May Promote Eosinophilic CRSwNP Progression by Enhancing Eosinophil Chemotaxis and Angiogenesis Under a Type 2 Inflammatory Milieu.International forum of allergy & rhinology · 2026Article
- Climate Change-Mediated Temperature Extremes: Effects on the Immune System and Associations with Immune-Related Diseases.Clinical reviews in allergy & immunology · 2026Review
- Role of Probiotics in Colitis Management: Mechanisms and Therapeutic Potential from Animal Studies.Probiotics and antimicrobial proteins · 2026Review
- Inhalable bioadhesive barrier for lung protection and clearance of fine particulate matter.Bioactive materials · 2026Article
- Mendelian randomization analysis of the causal relationship between allergic rhinitis and depression and underlying mediation mechanisms.The World Allergy Organization journal · 2026Article
- Impacts of Environmental Pollutants on Innate Immunity: The Role of Group 2 Innate Lymphoid Cells.Clinical reviews in allergy & immunology · 2026Review
- Association Between Serum Leptin Concentrations and Disease Severity Across Airway Disease Phenotypes: A Single-Center Retrospective Observational Study.Diseases (Basel, Switzerland) · 2026Article
- Dietary Adjuvanticity in the Modern Plant Exposome: Implications for Immune-Mediated Inflammatory Diseases.Nutrients · 2026Review
- Fucosyltransferases in asthma: regulators of epithelial dysfunction, senescence, and airway inflammation.Clinical reviews in allergy & immunology · 2026Review
- Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026Review
437 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There has been a steep increase in allergic and autoimmune diseases, reaching epidemic proportions and now affecting more than one billion people worldwide. These diseases are more common in industrialized countries, and their prevalence continues to rise in developing countries in parallel to urbanization and industrialization. Intact skin and mucosal barriers are crucial for the maintenance of tissue homeostasis as they protect host tissues from infections, environmental toxins, pollutants and allergens. A defective epithelial barrier has been demonstrated in allergic and autoimmune conditions such as asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, coeliac disease and inflammatory bowel disease. In addition, leakiness of the gut epithelium is also implicated in systemic autoimmune and metabolic conditions such as diabetes, obesity, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and autoimmune hepatitis. Finally, distant inflammatory responses due to a 'leaky gut' and microbiome changes are suspected in Alzheimer disease, Parkinson disease, chronic depression and autism spectrum disorders. This article introduces an extended 'epithelial barrier hypothesis', which proposes that the increase in epithelial barrier-damaging agents linked to industrialization, urbanization and modern life underlies the rise in allergic, autoimmune and other chronic conditions. Furthermore, it discusses how the immune responses to dysbiotic microbiota that cross the damaged barrier may be involved in the development of these diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.