ArticleCellular and molecular gastroenterology and hepatology2020
Tissue Responses to Shiga Toxin in Human Intestinal Organoids.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Ribosome-inactivating proteins in bacteria.Microbial genomics · 2026Review
- A barrier-centered perspective on the gut-barrier-bone axis: a review of the core role of the intestinal barrier and related probiotics with nanocoatings.Archives of microbiology · 2026Review
- Human Organoids and Organ-on-Chip for Biotoxin Assessment: Applications, Best Practices, and a Translational Roadmap.Toxins · 2026Review
- Intestinal mucosal barrier injury: insights from interdisciplinary perspectives and therapeutic approaches.Frontiers in nutrition · 2026Review
- Advanced Three-Dimensional Cell Culture Models for Investigating EnterohaemorrhagicJournal of microbiology and biotechnology · 2025Review
- More than a leaky gut: how gut priming shapes arthritis.Nature reviews. Rheumatology · 2025Review
- Advanced Animal Replacement Testing Strategies Using Stem Cell and Organoids.International journal of stem cells · 2025Review
- The Use of Gut Organoids: To Study the Physiology and Disease of the Gut Microbiota.Journal of cellular and molecular medicine · 2025Review
- Biomedical applications of organoids derived from the digestive system.Frontiers in cell and developmental biology · 2025Review
- Human pluripotent stem cell-derived organoids repair damaged bowel in vivo.Cell stem cell · 2024Article
- Article
- Translocation across a human enteroid monolayer by zoonoticiScience · 2024Article
- Intestinal barrier permeability: the influence of gut microbiota, nutrition, and exercise.Frontiers in physiology · 2024Review
- Targeting Gut Dysbiosis and Microbiome Metabolites for the Development of Therapeutic Modalities for Neurological Disorders.Current neuropharmacology · 2024Article
- Enzymatic Cleavage of Stx2a in the Gut and Identification of Pancreatic Elastase and Trypsin as Possible Main Cleavers.Microorganisms · 2023Article
- Morphological alterations in C57BL/6 mouse intestinal organoids as a tool for predicting chemical-induced toxicity.Archives of toxicology · 2023Article
- Shiga Toxin (Stx) Type 1a and Stx2a Translocate through a Three-Layer Intestinal Model.Toxins · 2023Article
- Review
- Applications of human organoids in the personalized treatment for digestive diseases.Signal transduction and targeted therapy · 2022Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsShiga toxin (Stx)-producing Escherichia coli (eg, O157:H7) infection produces bloody diarrhea, while Stx inhibits protein synthesis and causes the life-threatening systemic complication of hemolytic uremic syndrome. The murine intestinal tract is resistant to O157:H7 and Stx, and human cells in culture fail to model the complex tissue responses to intestinal injury. We used genetically identical, human stem cell-derived intestinal tissues of varying complexity to study Stx toxicity in vitro and in vivo.
methodsIn vitro susceptibility to apical or basolateral exposure to Stx was assessed using human intestinal organoids (HIOs) derived from embryonic stem cells, or enteroids derived from multipotent intestinal stem cells. HIOs contain a lumen, with a single layer of differentiated epithelium surrounded by mesenchymal cells. Enteroids only contain epithelium. In vivo susceptibility was assessed using HIOs, with or without an enteric nervous system, transplanted into mice.
resultsStx induced necrosis and apoptotic death in both epithelial and mesenchymal cells. Responses that require protein synthesis (cellular proliferation and wound repair) also were observed. Epithelial barrier function was maintained even after epithelial cell death was seen, and apical to basolateral translocation of Stx was seen. Tissue cross-talk, in which mesenchymal cell damage caused epithelial cell damage, was observed. Stx induced mesenchymal expression of the epithelial marker E-cadherin, the initial step in mesenchymal-epithelial transition. In vivo responses of HIO transplants injected with Stx mirrored those seen in vitro.
conclusionsIntestinal tissue responses to protein synthesis inhibition by Stx are complex. Organoid models allow for an unprecedented examination of human tissue responses to a deadly toxin.
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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.