ArticleAnnals of the New York Academy of Sciences2017
Zonulin transgenic mice show altered gut permeability and increased morbidity/mortality in the DSS colitis model.
Article in Annals of the New York Academy of Sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis.Nutrients · 2020Pooled it
- Effects of a multispecies synbiotic on glucose metabolism, lipid marker, gut microbiome composition, gut permeability, and quality of life in diabesity: a randomized, double-blind, placebo-controlled pilot study.European journal of nutrition · 2020Trial
- Combined Prebiotic Extract of Mung Bean, Red Bean, and Fennel Improves Intestinal Barrier Integrity in HT-29 Cells and DSS-Induced Colitis via Gut Microbiota Alteration.Current issues in molecular biology · 2025Article
- CharacterizingInternational journal of molecular sciences · 2025Article
- Multi-omics insight into the molecular networks of mental disorder related genetic pathways in the pathogenesis of inflammatory bowel disease.Translational psychiatry · 2025Article
- Predictive value of plasma zonulin for postoperative Hirschsprung-associated enterocolitis.World journal of pediatric surgery · 2025Article
- Elucidating the Significance of Zonulin in the Pathogenesis of Chronic Inflammatory Disorders: Emphasis on Intestinal Barrier Function and Tight Junction Regulation.Current medicinal chemistry · 2025Review
- Intestinal permeability disturbances: causes, diseases and therapy.Clinical and experimental medicine · 2024Review
- Unveiling the Novel Benefits of Co-Administering Butyrate and Active Vitamin D3 in Mice Subjected to Chemotherapy-Induced Gut-DerivedBiomedicines · 2024Article
- Article
- The Hazards of Probiotics on Gut-DerivedBiomedicines · 2024Article
- Prediction of gestational diabetes mellitus and perinatal outcomes by plasma zonulin levels.Archives of gynecology and obstetrics · 2024Article
- The epithelium takes the stage in asthma and inflammatory bowel diseases.Frontiers in cell and developmental biology · 2024Review
- Microbial interventions in yak colibacillosis: Lactobacillus-mediated regulation of intestinal barrier.Frontiers in cellular and infection microbiology · 2024Article
- Intestinal permeability in patients undergoing stem cell transplantation correlates with systemic acute phase responses and dysbiosis.Blood advances · 2023Article
- Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions.International journal of molecular sciences · 2023Review
- Assessing Gluten-Free Soy Bread Quality and Amino Acid Content.Foods (Basel, Switzerland) · 2023Article
- Ozoile Reduces the LPS-Induced Inflammatory Response in Colonic Epithelial Cells and THP-1 Monocytes.Current issues in molecular biology · 2023Article
- Article
- Prebiotic mechanisms of resistant starches from dietary beans and pulses on gut microbiome and metabolic health in a humanized murine model of aging.Frontiers in nutrition · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Increased small intestinal permeability (IP) has been proposed to be an integral element, along with genetic makeup and environmental triggers, in the pathogenies of chronic inflammatory diseases (CIDs). We identified zonulin as a master regular of intercellular tight junctions linked to the development of several CIDs. We aim to study the role of zonulin-mediated IP in the pathogenesis of CIDs. Zonulin transgenic Hp2 mice (Ztm) were subjected to dextran sodium sulfate (DSS) treatment for 7 days, followed by 4-7 days' recovery and compared to C57Bl/6 (wild-type (WT)) mice. IP was measured in vivo and ex vivo, and weight, histology, and survival were monitored. To mechanistically link zonulin-dependent impairment of small intestinal barrier function with clinical outcome, Ztm were treated with the zonulin inhibitor AT1001 added to drinking water in addition to DSS. We observed increased morbidity (more pronounced weight loss and colitis) and mortality (40-70% compared with 0% in WT) at 11 days post-DSS treatment in Ztm compared with WT mice. Both in vivo and ex vivo measurements showed an increased IP at baseline in Ztm compared to WT mice, which was exacerbated by DSS treatment and was associated with upregulation of zonulin gene expression (fourfold in the duodenum, sixfold in the jejunum). Treatment with AT1001 prevented the DSS-induced increased IP both in vivo and ex vivo without changing zonulin gene expression and completely reverted morbidity and mortality in Ztm. Our data show that zonulin-dependent small intestinal barrier impairment is an early step leading to the break of tolerance with subsequent development of CIDs.
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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.