ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2020
Liver Injury Impaired 25-Hydroxylation of Vitamin D Suppresses Intestinal Paneth Cell defensins, leading to Gut Dysbiosis and Liver Fibrogenesis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Association between serum 25-hydroxyvitamin D concentrations and overactive bladder in female: a mediation analysis of inflammatory biomarkers.Frontiers in nutrition · 2026Article
- Vitamin D screening and targeted supplementation delays liver fibrosis in patients with chronic liver disease: A prospective randomized controlled trial.Frontiers in medicine · 2026Article
- The Vitamin D-Gut-Brain Axis in Autism Spectrum Disorder: A Bidirectional Crosstalk.International journal of general medicine · 2026Review
- The Vicious Circle of Metabolic Dysfunction-Associated Steatotic Liver Disease When Micronutrient Deficiency Drives Microbial Imbalance and Liver Injury.Life (Basel, Switzerland) · 2025Review
- Associations of Serum Vitamin D with Sarcopenia in Patients with Chronic Liver Disease: A Population-Based Cross-Sectional Study.Calcified tissue international · 2025Article
- Gut-X Axis and Its Role in Poultry Bone Health: A Review.Microorganisms · 2025Review
- Clinical features and risk factors for combinedWorld journal of hepatology · 2025Article
- Non-targeted LC-MS metabolomics reveals serum metabolites for high-altitude adaptation in Tibetan donkeys.Scientific reports · 2025Article
- Nonlinear associations of serum vitamin D levels with advanced liver disease and mortality: a US Cohort Study.Therapeutic advances in gastroenterology · 2025Article
- Short-term treatment with cholestyramine increases long-acting anticoagulant rodenticide clearance from rabbits without affecting plasma vitamin K1 levels or blood coagulation.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Novel Mechanistic Insights.International journal of molecular sciences · 2024Review
- Vitamin A- and D-Deficient Diets Disrupt Intestinal Antimicrobial Peptide Defense Involving Wnt and STAT5 Signaling Pathways in Mice.Nutrients · 2023Article
- Reduced DEFA5 Expression and STAT3 Activation Underlie the Submucosal Invasion of Early Gastric Cancers.Digestion · 2023Article
- Multifaceted involvements of Paneth cells in various diseases within intestine and systemically.Frontiers in immunology · 2023Review
- Dietary Supplementation of 25-Hydroxyvitamin DAntioxidants (Basel, Switzerland) · 2022Article
- Plant green pigment of chlorophyllin attenuates inflammatory bowel diseases by suppressing autophagy activation in mice.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Vitamin D-VDR Novel Anti-Inflammatory Molecules-New Insights into Their Effects on Liver Diseases.International journal of molecular sciences · 2022Review
- Article
- The Role of Vitamin D in Immune System and Inflammatory Bowel Disease.Journal of inflammation research · 2022Review
- Review
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Authors and funding
13 authors at 6 institutions in 2 countries.
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Abstract
Vitamin D deficiency is co-prevalent with various liver diseases including cirrhosis, while the underlying mechanism remains elusive. Vitamin D receptor (VDR) is abundantly expressed in the distal region of small intestine, where the Paneth cells are enriched, suggesting that vitamin D signaling may modulates the intestinal Paneth cells and their production of defensins to restrain microbiome growth in the small intestine. In this study we found that in carbon tetrachloride-induced liver injury, hepatic 25-hydroxylation of vitamin D was impaired, leading to down regulated expression of Paneth cell fensins in the small intestine, gut dysbiosis, and endotoxinemia. While intraperitoneal injection of endotoxin (lipopolysaccharides) alone did not elicit liver fibrosis, it exacerbated the carbon tetrachloride initiated liver fibrogenesis. Oral gavage of synthetic Paneth cell alpha-defensin 5 (DEFA5) restored the homeostasis of gut microbiota, reduced endotoxemia, relieved liver inflammation, and ameliorated liver fibrosis. Likewise, Cholestyramine, cationic resin that can sequestrate endotoxin in the intestine, attenuated the liver fibrosis as well. Fecal transplant of the microbes derived from the DEFA5-treated donors improved liver fibrosis in the recipient mice. The intestinal Vdrconditional knockout mice exhibited reduction of Paneth cell defensins and lysozyme production, and worsened liver injury and fibrogenesis. Thus, liver injury impairs synthesis of 25(OH)VD
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