ArticleFrontiers in physiology2016
Vitamin D Signaling through Induction of Paneth Cell Defensins Maintains Gut Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal Models.
Article in Frontiers in physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.
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Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 186 citations in OpenAlex.
- Vitamin D and the gut microbiome: a systematic review of in vivo studies.European journal of nutrition · 2019Pooled it
- Maternal PMParticle and fibre toxicology · 2026Article
- Synergistic Anticancer Effects of Vitamin D and Plant-Derived Compounds: Molecular Mechanisms, Therapeutic Potential, and Nanotechnology-Enabled Delivery Approaches.International journal of molecular sciences · 2026Review
- Microbiome dysbiosis and its modulation in cancer development, prevention and therapy.Frontiers in oncology · 2026Review
- The role of gut microbiota in osteoporosis: underlying mechanisms, clinical associations, and emerging biomaterials.Frontiers in immunology · 2026Review
- Exploring the multifaceted roles of beta-defensins in prediabetes: a detailed review.Frontiers in endocrinology · 2026Review
- Disentangling the impact of obesity, diet, host factors, and microbiota on small intestinal antimicrobial peptide expression.Gut microbes · 2025Article
- Gut microbiota and associated metabolites: key players in high-fat diet-induced chronic diseases.Gut microbes · 2025Review
- Modelling the influence of vitamin D and probiotics on inflammation and the intestinal microbiota in older adults.Scientific reports · 2025Article
- Dietary Modulation of Metabolic Health: From Bioactive Compounds to Personalized Nutrition.Metabolites · 2025Review
- Exploring the link between fat-soluble vitamins and aging-associated immune system status: a literature review.Immunity & ageing : I & A · 2025Review
- Status and outlook of pulmonary tuberculosis coinfection.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2025Review
- 1,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat model.Frontiers in endocrinology · 2025Article
- Vitamin D supplementation alleviates high fat diet-induced metabolic associated fatty liver disease by inhibiting ferroptosis pathway.European journal of nutrition · 2024Article
- Goblet cells: guardians of gut immunity and their role in gastrointestinal diseases.eGastroenterology · 2024Article
- Nutraceuticals and pharmacological to balance the transitional microbiome to extend immunity during COVID-19 and other viral infections.Journal of translational medicine · 2024Review
- Supplementation of Vitamin DNutrients · 2024Article
- Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Novel Mechanistic Insights.International journal of molecular sciences · 2024Review
- Strain specific differences in vitamin D3 response: impact on gut homeostasis.Frontiers in immunology · 2024Article
- The Diagnostic Value of Human Neutrophilic Peptides 1-3 in Acute Pediatric Febrile Illness.Journal of clinical medicine · 2023Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD), is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis. Vitamin D receptor (VDR) is highly expressed in the ileum of the small intestine, which prompted us to test a hypothesis that vitamin D signaling may determine the enterotype of gut microbiota through regulating the intestinal interface. Here, we demonstrate that high-fat-diet feeding (HFD) is necessary but not sufficient, while additional vitamin D deficiency (VDD) as a second hit is needed, to induce robust insulin resistance and fatty liver. Under the two hits (HFD+VDD), the Paneth cell-specific alpha-defensins including α-defensin 5 (DEFA5), MMP7 which activates the pro-defensins, as well as tight junction genes, and MUC2 are all suppressed in the ileum, resulting in mucosal collapse, increased gut permeability, dysbiosis, endotoxemia, systemic inflammation which underlie insulin resistance and hepatic steatosis. Moreover, under the vitamin D deficient high fat feeding (HFD+VDD),
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