ArticleInflammatory bowel diseases2022
Eicosatetraynoic Acid and Butyrate Regulate Human Intestinal Organoid Mitochondrial and Extracellular Matrix Pathways Implicated in Crohn's Disease Strictures.
Article in Inflammatory bowel diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Gut microbiota-derived metabolites and host interactions in fibrotic diseases: mechanisms, cross-organ signatures, and therapeutic opportunities.Frontiers in microbiology · 2026Review
- Beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD?Annals of medicine · 2025Review
- Gut Microbiota as a Mediator Between Intestinal Fibrosis and Creeping Fat in Crohn's Disease.United European gastroenterology journal · 2025Review
- Host-microbiome relationship in depression: can human induced pluripotent stem cells play a role in unravelling mechanisms?NPJ biofilms and microbiomes · 2025Review
- Advances and applications of gut organoids: modeling intestinal diseases and therapeutic development.Life medicine · 2025Review
- 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
- Multiomics reveals microbial metabolites as key actors in intestinal fibrosis in Crohn's disease.EMBO molecular medicine · 2024Article
- Challenges and opportunities in inflammatory bowel disease: from current therapeutic strategies to organoid-based models.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Gastrointestinal tract organoids as novel tools in drug discovery.Frontiers in pharmacology · 2024Review
- Crohn's disease: Why the ileum?World journal of gastroenterology · 2023Review
- Mucosa-AssociatedMicroorganisms · 2023Article
- Induced Pluripotent Stem Cell-Derived Organoids: Their Implication in COVID-19 Modeling.International journal of molecular sciences · 2023Review
- Fatty acids and lipid mediators in inflammatory bowel disease: from mechanism to treatment.Frontiers in immunology · 2023Review
- Approaches to investigating metabolism in human neurodevelopment using organoids: insights from intestinal and cancer studies.Development (Cambridge, England) · 2022Article
- Review
- Novel Models of Crohn's Disease Pathogenesis Associated with the Occurrence of Mitochondrial Dysfunction in Intestinal Cells.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundPerturbagen analysis of Crohn's disease (CD) ileal gene expression data identified small molecules including eicosatetraynoic acid (ETYA), which may exert an antifibrotic effect. We developed a patient-specific human intestinal organoid (HIO) model system to test small molecule regulation of mitochondrial and wound-healing functions implicated in stricturing behavior.
methodsHIOs were made from CD induced pluripotent stem cells with and without a loss-of-function haplotype in the DUOX2 gene implicated in ileal homeostasis and characterized under basal conditions and following exposure to butyrate and ETYA using RNA sequencing, flow cytometry, and immunofluorescent and polarized light microscopy. Mitochondrial activity was measured using high-resolution respirometry and tissue stiffness using atomic force microscopy.
resultsHIOs expressed core mitochondrial and extracellular matrix (ECM) genes and enriched biologic functions implicated in CD ileal strictures; ECM gene expression was suppressed by both butyrate and ETYA, with butyrate also suppressing genes regulating epithelial proliferation. Consistent with this, butyrate, but not ETYA, exerted a profound effect on HIO epithelial mitochondrial function, reactive oxygen species production, and cellular abundance. Butyrate and ETYA suppressed HIO expression of alpha smooth muscle actin expressed by myofibroblasts, type I collagen, and collagen protein abundance. HIOs exhibited tissue stiffness comparable to normal human ileum; this was reduced by chronic ETYA exposure in HIOs carrying the DUOX2 loss-of-function haplotype.
conclusionsETYA regulates ECM genes implicated in strictures and suppresses collagen content and tissue stiffness in an HIO model. HIOs provide a platform to test personalized therapeutics, including small molecules prioritized by perturbagen analysis.
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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.