ArticleThe Journal of clinical investigation2021
DUOX2 variants associate with preclinical disturbances in microbiota-immune homeostasis and increased inflammatory bowel disease risk.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 76 citations in OpenAlex.
- Toll-like receptor 2 impacts small intestinal villus capillarization through epithelial dual oxidase 2.Redox biology · 2026Article
- An IL-17-DUOX2 axis controls gastrointestinal colonization by Candida albicans.Nature communications · 2026Article
- Article
- DUOX2-Driven Oxidative Stress Alters the Gut Redox Niche and Promotes Microbial Dysbiosis in Crohn's Disease.Antioxidants (Basel, Switzerland) · 2026Article
- Monogenic forms of inflammatory bowel disease: Genetic mechanisms, models, and clinical implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Ultrarare Variants in DNA Damage Repair and Mitochondrial Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome and Acute Behavioral Regression in Neurodevelopmental Disorders.Developmental neuroscience · 2026Article
- Dictionary of human intestinal organoid responses to secreted niche factors at single cell resolution.Nature communications · 2026Article
- Selenium: A Key Element in Inflammatory Bowel Disease.Antioxidants (Basel, Switzerland) · 2025Review
- The microbiome in cancer.iMeta · 2025Review
- Comprehensive analysis of heterogeneity and cell-cell interactions in Crohn's disease reveals novel location-specific insights.Journal of advanced research · 2025Article
- Construction of a feature gene and machine prediction model for inflammatory bowel disease based on multichip joint analysis.Journal of translational medicine · 2025Article
- Spatiotemporal HNature communications · 2025Article
- Transmission of maternal oral pathobionts to the infant gut predisposes offspring to exacerbated enteritis.Cell reports · 2025Article
- Endoscopic healing in pediatric IBD perpetuates a persistent signature defined by Th17 cells with molecular and microbial drivers of disease.Cell reports. Medicine · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Advances in Understanding Intestinal Homeostasis: Lessons from Inflammatory Bowel Disease and Monogenic Intestinal Disorder Pathogenesis.International journal of molecular sciences · 2025Review
- Article
- De novo DUOX2 expression in neutrophil subsets shapes the pathogenesis of intestinal disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Eicosatetraynoic Acid Regulates Profibrotic Pathways in an Induced Pluripotent Stem Cell-Derived Macrophage-Human Intestinal Organoid Model of Crohn's Disease.Journal of Crohn's & colitis · 2025Article
- A multi-omics spatial framework for host-microbiome dissection within the intestinal tissue microenvironment.Nature communications · 2025Article
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
Abstract
A primordial gut-epithelial innate defense response is the release of hydrogen peroxide by dual NADPH oxidase (DUOX). In inflammatory bowel disease (IBD), a condition characterized by an imbalanced gut microbiota-immune homeostasis, DUOX2 isoenzyme is the highest induced gene. Performing multiomic analyses using 2872 human participants of a wellness program, we detected a substantial burden of rare protein-altering DUOX2 gene variants of unknown physiologic significance. We identified a significant association between these rare loss-of-function variants and increased plasma levels of interleukin-17C, which is induced also in mucosal biopsies of patients with IBD. DUOX2-deficient mice replicated increased IL-17C induction in the intestine, with outlier high Il17c expression linked to the mucosal expansion of specific Proteobacteria pathobionts. Integrated microbiota/host gene expression analyses in patients with IBD corroborated IL-17C as a marker for epithelial activation by gram-negative bacteria. Finally, the impact of DUOX2 variants on IL-17C induction provided a rationale for variant stratification in case control studies that substantiated DUOX2 as an IBD risk gene. Thus, our study identifies an association of deleterious DUOX2 variants with a preclinical hallmark of disturbed microbiota-immune homeostasis that appears to precede the manifestation of IBD.
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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.