ArticleiScience2023
SCFAs switch stem cell fate through HDAC inhibition to improve barrier integrity in 3D intestinal organoids from patients with obesity.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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
29 citing papers in PubMed, 30 citations in OpenAlex.
- Review
- Dietary Regulation of Intestinal Stem Cell Function: Nutrient-Sensing, Microbiota-Mediated, and Regenerative Mechanisms from a Dietetic Perspective.Biomedicines · 2026Review
- RUNX2 promotes chromatin accessibility and WNT signaling in inflamed intestinal epithelial cells.Mucosal immunology · 2026Article
- Virgin Coconut Oil Attenuates Diabetic Kidney Disease via Gut Microbiota-Metabolism-Inflammation Axis Modulation in Type 2 Diabetic Mice.Food science & nutrition · 2026Article
- Stage-dependent effects of composite probiotics on gut mineral transport, Skeletal health, and egg quality in laying hens.Poultry science · 2026Article
- Cannabidiol triggers fatty acids β-oxidation mediated by Stat2 to facilitate intestinal stem cells regeneration post radiation.Experimental & molecular medicine · 2026Article
- Microbial regulation of intestinal stem cell function: implications for alleviating intestinal injury of weaned piglets.NPJ biofilms and microbiomes · 2026Review
- Host-microbiome interactions in leukemia: mechanisms, treatment response, and clinical implications.Frontiers in cellular and infection microbiology · 2026Review
- Gut microbiota-epigenetic interactions in systemic aging: mechanistic drivers for endocrine and reproductive network remodeling and therapeutic modulation.Frontiers in aging · 2026Review
- Nutrition as a systems regulator of brain aging trajectories.Frontiers in molecular neuroscience · 2026Review
- Gut microbiota-derived metabolites in gastrointestinal cancer: immunomodulatory mechanisms via the tryptophan-AhR axis and translational perspectives.Frontiers in immunology · 2026Review
- Review
- FFAR4 drives stem cell fate toward lipid- and iron-storing enterocytes protecting human enteroids from ferroptosis.Stem cell research & therapy · 2025Article
- HarnessingGut microbes · 2025Article
- RUNX2 promotes epigenetic WNT signaling in inflamed intestinal epithelial cells.bioRxiv : the preprint server for biology · 2025Article
- Akkermansia muciniphila: a microbial guardian against oxidative stress-gut microbiota crosstalk and clinical prospects.Journal of translational medicine · 2025Review
- Potential roles of histone deacetylases in diabetic wound healing.World journal of diabetes · 2025Review
- The Use of Organoid Cultures in Advancing Nutrition Research.Advances in nutrition (Bethesda, Md.) · 2025Review
- Microbiome-derived metabolites in cancer-associated anemia: An underexplored mechanistic link.World journal of gastrointestinal pharmacology and therapeutics · 2025Article
- PCOS endometrium-derived epithelial organoids as a novel model to study endometrial dysfunction.Human reproduction (Oxford, England) · 2025Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stem cells are a keystone of intestinal homeostasis, but their function could be shifted during energy imbalance or by crosstalk with microbial metabolites in the stem cell niche. This study reports the effect of obesity and microbiota-derived short-chain fatty acids (SCFAs) on intestinal stem cell (ISC) fate in human crypt-derived intestinal organoids (enteroids). ISC fate decision was impaired in obesity, resulting in smaller enteroids with less outward protruding crypts. Our key finding is that SCFAs switch ISC commitment to the absorptive enterocytes, resulting in reduced intestinal permeability in obese enteroids. Mechanistically, SCFAs act as HDAC inhibitors in stem cells to enhance Notch signaling, resulting in transcriptional activation of the Notch target gene HES1 to promote enterocyte differentiation. In summary, targeted reprogramming of ISC fate, using HDAC inhibitors, may represent a potential, robust therapeutic strategy to improve gut integrity in obesity.
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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.