ArticleInfection and immunity2016
Intestinal Enteroids Model Guanylate Cyclase C-Dependent Secretion Induced by Heat-Stable Enterotoxins.
Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Human Organoids and Organ-on-Chip for Biotoxin Assessment: Applications, Best Practices, and a Translational Roadmap.Toxins · 2026Review
- Baicalin: Natural Sources, Extraction Techniques, and Therapeutic Applications Against Bacterial Infections.Molecules (Basel, Switzerland) · 2025Review
- Immunotherapy for precision medicine in colorectal cancer.Expert review of precision medicine and drug development · 2025Article
- Advancements in understanding bacterial enteritis pathogenesis through organoids.Molecular biology reports · 2024Review
- GUCY2C signaling limits dopaminergic neuron vulnerability to toxic insults.NPJ Parkinson's disease · 2024Article
- Microbiota-derived butyrate dampens linaclotide stimulation of the guanylate cyclase C pathway in patient-derived colonoids.Neurogastroenterology and motility · 2023Article
- Fundamental Neurochemistry Review: The role of enteroendocrine cells in visceral pain.Journal of neurochemistry · 2023Review
- Human intestinal organoids as models to study enteric bacteria and viruses.Current opinion in microbiology · 2023Review
- Intestinal neuropod cell GUCY2C regulates visceral pain.The Journal of clinical investigation · 2023Article
- Targeting gastrointestinal cancers with chimeric antigen receptor (CAR)-T cell therapy.Cancer biology & therapy · 2022Article
- Guanylyl cyclase C as a diagnostic and therapeutic target in colorectal cancer.Personalized medicine · 2022Review
- EnterotoxigenicInfection and immunity · 2022Article
- Diarrheal pathogens trigger rapid evolution of the guanylate cyclase-C signaling axis in bats.Cell host & microbe · 2021Article
- [Changes of guanylate cyclase C in colon tissues of rats with intestinal injury associated with severe acute pancreatitis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer.Expert review of clinical pharmacology · 2020Review
- Human Intestinal Enteroids With Inducible Neurogenin-3 Expression as a Novel Model of Gut Hormone Secretion.Cellular and molecular gastroenterology and hepatology · 2019Article
- Linaclotide improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium/hydrogen exchanger 3.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Review
- Article
- Acidosis potentiates endothelium-dependent vasorelaxation and gap junction communication in the superior mesenteric artery.European journal of pharmacology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Enterotoxigenic Escherichia coli (ETEC) causes ∼20% of the acute infectious diarrhea (AID) episodes worldwide, often by producing heat-stable enterotoxins (STs), which are peptides structurally homologous to paracrine hormones of the intestinal guanylate cyclase C (GUCY2C) receptor. While molecular mechanisms mediating ST-induced intestinal secretion have been defined, advancements in therapeutics have been hampered for decades by the paucity of disease models that integrate molecular and functional endpoints amenable to high-throughput screening. Here, we reveal that mouse and human intestinal enteroids in three-dimensional ex vivo cultures express the components of the GUCY2C secretory signaling axis. ST and its structural analog, linaclotide, an FDA-approved oral secretagog, induced fluid accumulation quantified simultaneously in scores of enteroid lumens, recapitulating ETEC-induced intestinal secretion. Enteroid secretion depended on canonical molecular signaling events responsible for ETEC-induced diarrhea, including cyclic GMP (cGMP) produced by GUCY2C, activation of cGMP-dependent protein kinase (PKG), and opening of the cystic fibrosis transmembrane conductance regulator (CFTR). Importantly, pharmacological inhibition of CFTR abrogated enteroid fluid secretion, providing proof of concept for the utility of this model to screen antidiarrheal agents. Intestinal enteroids offer a unique model, integrating the GUCY2C signaling axis and luminal fluid secretion, to explore the pathophysiology of, and develop platforms for, high-throughput drug screening to identify novel compounds to prevent and treat ETEC diarrheal disease.
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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.