Vitamin D Receptor Influences Intestinal Barriers in Health and Disease

Sun, Jun; Zhang, Yongguo

doi:10.3390/cells11071129

Cited by 32 publications

(20 citation statements)

References 176 publications

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“…In fact, approximately 3% of the mouse and human genomes are directly or indirectly regulated by vitamin D, suggesting a broad contribution of vitamin D/VDR in diverse disease mechanisms ( 43 , 44 ). For several organ dysfunctions, the vitamin D/VDR signaling pathway is essential in regulating connectivity components and maintaining epithelial barrier integrity, including intestinal inflammation, infection, and chronic inflammatory lung diseases ( 45 ). It was previously proposed that the main mechanism by which VDR activation affected autoimmunity was through genetic activation of myeloid immune cells, particularly antigen-presenting dendritic cells (DCs), thereby triggering a tolerance status in the immune system, particularly in DCs ( 46 , 47 ).…”

Section: Discussionmentioning

confidence: 99%

Visual analysis of the research trend and status on the association between vitamin D and immunity: From 2012 to 2021

Luo

Deng

2022

Front. Nutr.

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ObjectiveWe conducted this study to visualize hot spots and trends in the correlation between vitamin D and immunity over the past decade with bibliometric analysis.MethodsWe collected relevant articles in the Web of Science Core Collection from 2012 to 2021 as the data source, and then used CiteSpace software to perform the data analysis. Some graphics were done with Graphpad software.ResultsA total of 1,656 articles were retrieved, with an average citation count of 25.2 times. The United States (439 articles, 26.51%) has the top number of published articles, followed by China (164 articles, 9.90%), England (135 articles, 8.15%), Italy (114 articles, 6.88%), and India (82 articles, 4.95%). The most literature is found in areas of Immunology (337 articles, 20.35%) and Biochemistry Molecular Biology (179 articles, 10.81%). In terms of institutions, the top five institutions with the highest number of publications all belong to Europe. Among them, the League of European Research Universities (LERU) (121, 7.31%) has a greater proportion of output articles. The United States Department of Health Human Services (225, 13.59%) and National Institutes of Health United States (223, 13.47%) funded most articles. The leading five authors with the largest number of publications were Hewison M (19, 1.15%), Bergman P (14, 0.85%), Agerberth B (13, 0.76%), Carlberg C (12, 0.73%), and White JH (12, 0.73%). The top five keywords with the highest co-occurrence frequency are “vitamin d” (367), “d deficiency” (217), “expression” (195), “association” (151), and “d receptor” (132). Among the 17 keyword clusters, the largest cluster is #0 “diet.” Despite cluster #13 “covid-19,” most of the clusters were conducted the studies before 2012.ConclusionThe overall development of research in this field is promising. Western developed countries made outstanding contributions in this area and still take the leading role. But the participation of developing and low-income countries is also impressive. The potential therapeutic effects of vitamin D in immune-related diseases have been noted, especially in multiple sclerosis, COVID-19, etc. This is also the focus and frontier of current research. However, there is still no consensus conclusion in this field. Further research is needed in the future.

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Section: Discussionmentioning

confidence: 99%

Visual analysis of the research trend and status on the association between vitamin D and immunity: From 2012 to 2021

Luo

Deng

2022

Front. Nutr.

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“…Dysbiosis of the gut microbiome could indirectly participate in the development or progression of breast cancer via bacterial metabolites from the gut (SBA, SCFA, PAMPs, vitamin) and immune and inflammatory modulators (TLR, cytokines) that are inextricably interlinked with the microbiome from the GI tract 32 . VDR expression increases epithelial integrity and attenuates inflammation 52 . Interestingly, we found some butyrate-related modules were also Epidemiological and experimental studies have indicated a protective action of vitamin D against colorectal cancer [54][55][56][57][58][59][60] .…”

Section: Discussionmentioning

confidence: 99%

Extraintestinal roles of intestinal vitamin D receptor in protecting against dysbiosis and tumorigenesis in breast cancer

Zhang

Deb

et al. 2022

Preprint

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The microbiota play critical roles in regulating the function and health of intestine and extraintestinal organs. A fundamental question is whether there is an intestinal-microbiome-breast axis during the development of breast cancer. If yes, what are the roles of host factors? Vitamin D receptor (VDR) involves host factors and the human microbiome. Vdr gene variation shapes the human microbiome and VDR deficiency leads to dysbiosis. We hypothesized that intestinal VDR protects hosts against tumorigenesis in breast. Reduced VDR mRNA expression was observed in patients with breast cancer. We used a 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model in intestinal epithelial VDR knockout (VDRΔIEC) mice. We reported that VDRΔIEC mice with dysbiosis are more susceptible to breast cancer induced by DMBA. Intestinal and breast microbiota analysis showed that lacking VDR leads to bacterial profile shift from normal to susceptible carcinogenesis. We found enhanced bacterial staining within breast tumors. At the molecular and cellular levels, we identified the mechanisms by which intestinal epithelial VDR deficiency led to increased gut permeability, disrupted tight junctions, microbial translocation, and enhanced inflammation, thus increasing the tumor size and number in breast. Furthermore, treatment with beneficial bacterial metabolite butyrate or probiotic Lactobacillus plantarum reduced the breast tumors, enhanced the tight junctions, and inhibited inflammation in the VDRΔIEC mice. Gut microbiome contribute to the pathogenesis of diseases, not only in the intestine, but also in the breast. Our study provides new insights into the mechanism by which intestinal VDR dysfunction and gut dysbiosis led to high risk of extraintestinal tumorigenesis. Gut-tumor-microbiome interactions indicate a new target in the prevention and treatment of breast cancer.Abstract Figure

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“…It also inhibits transcription of ZO-1, claudin-5, and occludin genes and increases the tight junction protein claudin-2 which enhance intestinal permeability. Thus, lacking intestinal epithelial VDR regulation in inflamed intestine leads to hyperfunction of Claudin-2 and exaggerates the inflammatory responses in the intestines [ 47 ].…”

Section: Pleiotropic Effects Of Vitamin D In Inflammatory-based Diseasesmentioning

confidence: 99%

Genomic or Non-Genomic? A Question about the Pleiotropic Roles of Vitamin D in Inflammatory-Based Diseases

et al. 2023

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Vitamin D (vit D) is widely known for its role in calcium metabolism and its importance for the bone system. However, various studies have revealed a myriad of extra-skeletal functions, including cell differentiation and proliferation, antibacterial, antioxidant, immunomodulatory, and anti-inflammatory properties in various cells and tissues. Vit D mediates its function via regulation of gene expression by binding to its receptor (VDR) which is expressed in almost all cells within the body. This review summarizes the pleiotropic effects of vit D, emphasizing its anti-inflammatory effect on different organ systems. It also provides a comprehensive overview of the genetic and epigenetic effects of vit D and VDR on the expression of genes pertaining to immunity and anti-inflammation. We speculate that in the context of inflammation, vit D and its receptor VDR might fulfill their roles as gene regulators through not only direct gene regulation but also through epigenetic mechanisms.

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Vitamin D Receptor Influences Intestinal Barriers in Health and Disease

Cited by 32 publications

References 176 publications

Visual analysis of the research trend and status on the association between vitamin D and immunity: From 2012 to 2021

Visual analysis of the research trend and status on the association between vitamin D and immunity: From 2012 to 2021

Extraintestinal roles of intestinal vitamin D receptor in protecting against dysbiosis and tumorigenesis in breast cancer

Genomic or Non-Genomic? A Question about the Pleiotropic Roles of Vitamin D in Inflammatory-Based Diseases

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