Vitamin D in inflammatory bowel disease: From biology to clinical implications

Parizadeh, Seyed Mostafa; Jafarzadeh‐Esfehani, Reza; Hassanian, Seyed Mahdi; Mottaghi-Moghaddam, Ali; Ghazaghi, Anahita; Ghandehari, Maryam; Alizade-Noghani, Mohadese; Khazaei, Majid; Ferns, Gordon A.

doi:10.1016/j.ctim.2019.08.023

Cited by 23 publications

(19 citation statements)

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“…Numerous studies have linked vitamin D deficiency with increased risk of IBD, a major risk factor for development of CRC [53][54][55][56][57], although it is unclear whether this deficiency is a cause of IBD or a consequence. However, there is ample evidence supporting a role for the bioactive form of vitamin D, 1,25-dihydroxycholecalciferol (D 3 ), as a potent immune and inflammation modulator in the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

et al. 2020

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Consumption of a Western type diet is a known risk factor for colorectal cancer. Our group previously developed the total Western diet (TWD) for rodents with energy and nutrient profiles that emulate a typical Western diet. In this study, we tested the hypothesis that consumption of the TWD would enhance colitis, delay recovery from gut injury and promote colon tumorigenesis.In multiple experiments using the azoxymethane + dextran sodium sulfate or Apc Min/+ mouse models of colitis-associated colorectal carcinogenesis (CAC), we determined that mice fed TWD experienced more severe and more prolonged colitis compared to their counterparts fed the standard AIN93G diet, ultimately leading to markedly enhanced colon tumorigenesis. Additionally, this increased tumor response was attributed to the micronutrient fraction of the TWD, and restoration of calcium and vitamin D to standard amounts ameliorated the tumor-promoting effects of TWD. Finally, exposure to the TWD elicited large scale, dynamic changes in mRNA signatures of colon mucosa associated with interferon (IFN) response, inflammation, innate immunity, adaptive immunity, and antigen processing pathways, among others. Taken together, these observations indicate that consumption of the TWD markedly enhanced colitis, delayed recovery from gut injury, and enhanced colon tumorigenesis likely via extensive changes in expression of immune-related genes in the colon mucosa.Nutrients 2020, 12, 544 2 of 35 characterizes these conditions is now recognized as an important factor in CRC due to its involvement in the disruption of the same oncogenic pathways that are disrupted in CRC [5]. The mutation of genes involved in the maintenance of the intestinal mucosal barrier that protects the intestinal wall from bacterial invasion contributes to both Crohn's and UC [6,7].Dysfunction of the intestinal mucosal barrier leads to sustained damage of gut epithelial cells. This chronic injury to the gut triggers a compensatory immune response characterized by the up-regulation of cell proliferation and anti-apoptotic pathways that promote cell survival [8]. Various molecules are involved in the activation of such pathways, including transcription factors (e.g., NF-κB, and STAT3) and various inflammatory cytokines (e.g., IL-6 and TNF-α), which are normally secreted during an inflammatory response. The resulting compensatory cell regeneration results in increased rates of mitosis that, when chronically active, increase DNA mutation rates [8,9]. Not only can this process promote the disruption of oncogenic pathways, but it can also provide cancerous cells with a nurturing environment due to the increased availability of proliferative and survival signals. This notion is supported by an animal study by Tanaka et al. [10], in which a combined treatment of the chemical carcinogen azoxymethane (AOM) with the inflammatory agent dextran sodium sulfate (DSS) significantly increased intestinal tumorigenesis in CD-1 mice. The AOM + DSS model yields a consistent, reproducible colon cancer outcome ...

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Section: Discussionmentioning

confidence: 99%

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

et al. 2020

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“…Additionally, vitamin D can modulate both adaptive and innate immunity [ 191 ]. Indeed, vitamin D deficiency is associated with several autoimmune diseases [ 192 ], for example, rheumatoid arthritis (RA) [ 193 , 194 ], inflammatory bowel disease (IBD) [ 195 , 196 , 197 , 198 ] and multiple sclerosis (MS) [ 199 , 200 , 201 , 202 ]. Associations between low vitamin D status and autoimmune thyroid diseases and thyroid cancer were also found [ 203 ].…”

Section: Vitamin D: State Of the Artmentioning

confidence: 99%

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

Riccardi

Perrone

Napolitano

et al. 2020

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Vitamin D is a fat-soluble steroid hormone playing a pivotal role in calcium and phosphate homeostasis as well as in bone health. Vitamin D levels are not exclusively dependent on food intake. Indeed, the endogenous production—occurring in the skin and dependent on sun exposure—contributes to the majority amount of vitamin D present in the body. Since vitamin D receptors (VDRs) are ubiquitous and drive the expression of hundreds of genes, the interest in vitamin D has tremendously grown and its role in different diseases has been extensively studied. Several investigations indicated that vitamin D action extends far beyond bone health and calcium metabolism, showing broad effects on a variety of critical illnesses, including cancer, infections, cardiovascular and autoimmune diseases. Epidemiological studies indicated that low circulating vitamin D levels inversely correlate with cutaneous manifestations and bone abnormalities, clinical hallmarks of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumour predisposition syndrome causing significant pain and morbidity, for which limited treatment options are available. In this context, vitamin D or its analogues have been used to treat both skin and bone lesions in NF1 patients, alone or combined with other therapeutic agents. Here we provide an overview of vitamin D, its characteristic nutritional properties relevant for health benefits and its role in NF1 disorder. We focus on preclinical and clinical studies that demonstrated the clinical correlation between vitamin D status and NF1 disease, thus providing important insights into disease pathogenesis and new opportunities for targeted therapy.

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“…Clinical trials on vitamin D deficiency and IBD were yielding contradictory results concerning the development, disease activity and remission rate 1,2 . Meanwhile, the effect of vitamin D supplementation in treating IBD was also controversial 3,4 . The controversy might root in the different mechanisms between Crohn's disease (CD) and ulcerative colitis (UC), or even the diverse immunological sub-types of the two main categories.…”

Section: Introductionmentioning

confidence: 99%

Intestinal vitamin D receptor knockout protects from oxazolone-induced colitis

et al. 2020

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Crohn's disease (CD) and ulcerative colitis (UC) actually had different pathological mechanisms, as the former was mainly induced by Th1 and Th17 response and the latter by Th2 response. Our previous study found that oxazoloneinduced Th2-mediated colitis could not be attenuated by vitamin D supplementation. This study investigated the influence of intestinal vitamin D receptor (VDR) knockout on oxazolone-induced colitis and explored the possible immunological mechanism. Intestinal VDR knockout mice had milder oxazolone-induced colitis than wildtype controls, as demonstrated by less body weight decrease and faster recovery, more intact local structure, reduced cell apoptosis, and better preserved barrier function. Th2-mediated inflammation was significantly inhibited by VDR deficiency. Meanwhile, the percentage of invariant natural killer T (iNKT) cells did not increase as much in intestinal VDR knockout mice as in wild-type controls, nor did the iNKT cells develop normally as in the controls. Intestinal VDR knockout protected against oxazolone-induced colitis in mice by blocking Th2 cell response and reducing the function of intestinal iNKT cells. Vitamin D status had no influence on the severity of colitis. This study may explain the diverse outcomes after vitamin D supplementation in literature and add some clue to the targeted therapy of IBD.

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Vitamin D in inflammatory bowel disease: From biology to clinical implications

Cited by 23 publications

References 98 publications

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

Intestinal vitamin D receptor knockout protects from oxazolone-induced colitis

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