ArticleInternational journal of molecular sciences2022
Intestinal Stem Cells Damaged by Deoxycholic Acid via AHR Pathway Contributes to Mucosal Barrier Dysfunction in High-Fat Feeding Mice.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Effects and mechanism ofWorld journal of gastroenterology · 2026Article
- Mechanisms of multi-organ damage in Wilson disease from the gut-liver-brain axis perspective: copper metabolism, gut microbiota, and metabolite communication.Frontiers in microbiology · 2026Review
- Deoxycholic acid promotes anxiety- and depression-like behaviors in mice via modulation of the gut microbial metabolite indole-3-propionic acid.Frontiers in immunology · 2026Article
- Intestinal LGR4 Signalling Alters Bacterial translocation, Intrahepatic Microbiota composition, and Type 1 Interferon Expression in Murine Liver Fibrosis.Inflammation · 2025Article
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- The gut microbiota-bile acid axis: a crucial regulator of immune function and metabolic health.World journal of microbiology & biotechnology · 2025Review
- ABL1‒YAP1 axis in intestinal stem cell activated by deoxycholic acid contributes to hepatic steatosis.Journal of translational medicine · 2024Article
- Brain-Gut and Microbiota-Gut-Brain Communication in Type-2 Diabetes Linked Alzheimer's Disease.Nutrients · 2024Review
- Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis.Scientific reports · 2024Article
- Review
- Different Diet Energy Levels Alter Body Condition, Glucolipid Metabolism, Fecal Microbiota and Metabolites in Adult Beagle Dogs.Metabolites · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
High-fat exposure leads to impaired intestinal barrier function by disrupting the function of intestinal stem cells (ISCs); however, the exact mechanism of this phenomenon is still not known. We hypothesize that high concentrations of deoxycholic acid (DCA) in response to a high-fat diet (HFD) affect aryl hydrocarbon receptor (AHR) signalling in ISCs and the intestinal barrier. For this purpose, C57BL/6J mice feeding on a low-fat diet (LFD), an HFD, an HFD with the bile acid binder cholestyramine, and a LFD with the DCA were studied. We found that high-fat feeding induced an increase in faecal DCA concentrations. An HFD or DCA diet disrupted the differentiation function of ISCs by downregulating AHR signalling, which resulted in decreased goblet cells (GCs) and MUC2, and these changes were reversed by cholestyramine. In vitro experiments showed that DCA downregulated the differentiation function of ISCs, which was reversed by the AHR agonist 6-formylindolo [3,2-b]carbazole (FICZ). Mechanistically, DCA caused a reduction in indoleamine 2,3-dioxygenase 1 (IDO1) in Paneth cells, resulting in paracrine deficiency of the AHR ligand kynurenine in crypts. We demonstrated for the first time that DCA disrupts intestinal mucosal barrier function by interfering with AHR signalling in ISCs. Supplementation with AHR ligands may be a new therapeutic target for HFD-related impaired intestinal barrier function.
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Registered trials
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