Role of Vitamin D in Inflammatory Bowel Disease

Limketkai, Berkeley N.; Mullin, Gerard E.; Limsui, David; Parian, Alyssa

doi:10.1177/0884533616674492

Cited by 46 publications

(37 citation statements)

References 125 publications

(132 reference statements)

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“…The new actions of vitamin D described in this study may contribute to the homeostasis of healthy intestinal mucosa, and to the repair and regeneration of damaged intestine upon injury. In line with this, epidemiological studies indicate an association of vitamin D deficiency with IBD, and experiments with animal models suggest a beneficial effect of VDR agonists in these conditions [31].…”

Section: Discussionmentioning

confidence: 58%

“…Although Wnt and EGF pathways are essential for colon stem cell proliferation in vivo and, concordantly, for the generation of organoids in vitro [32,33], we show that calcitriol reduces cell proliferation in normal organoids, yet classical Wnt pathway genes were unaffected in our transcriptomic analyses. Instead, calcitriol upregulates LRIG1, marker of quiescent + 4 stem cells [21,31] and also master regulator of epithelial stem cells and tumor suppressor that encodes a multilevel tyrosine kinase receptor (EGFR and others) inhibitor [34,35]. Moreover, we observed in mouse, due the lack of the equivalent human signature, that calcitriol induces a gene expression profile that is related to the Mex3a high /Lgr5 high signature of slow-dividing intestinal stem cells [22].…”

Section: Discussionmentioning

confidence: 96%

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Vitamin D differentially regulates colon stem cells in patient‐derived normal and tumor organoids

et al. 2019

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Intestine is a major target of vitamin D and several studies indicate an association between vitamin D deficiency and inflammatory bowel diseases (IBD), but also increased colorectal cancer (CRC) risk and mortality. However, the putative effects of 1α,25‐dihydroxyvitamin D3 (calcitriol), the active vitamin D metabolite, on human colonic stem cells are unknown. Here we show by immunohistochemistry and RNAscope in situ hybridization that vitamin D receptor (VDR) is unexpectedly expressed in LGR5+ colon stem cells in human tissue and in normal and tumor organoid cultures generated from patient biopsies. Interestingly, normal and tumor organoids respond differentially to calcitriol with profound and contrasting changes in their transcriptomic profiles. In normal organoids, calcitriol upregulates stemness‐related genes, such as LGR5, SMOC2, LRIG1, MSI1, PTK7, and MEX3A, and inhibits cell proliferation. In contrast, in tumor organoids calcitriol has little effect on stemness‐related genes while it induces a differentiated phenotype, and variably reduces cell proliferation. Concordantly, electron microscopy showed that calcitriol does not affect the blastic undifferentiated cell phenotype in normal organoids but it induces a series of differentiated features in tumor organoids. Our results constitute the first demonstration of a regulatory role of vitamin D on human colon stem cells, indicating a homeostatic effect on colon epithelium with relevant implications in IBD and CRC.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 96%

Vitamin D differentially regulates colon stem cells in patient‐derived normal and tumor organoids

et al. 2019

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“…Vitamin D, or calciferol, is a generic term and refers to a group of lipid-soluble compounds, 25-OH-D being the major circulating form of vitamin D and 1,25-dihydroxyvitamin D (1,25[OH] 2 D) its most active form [27]. Vitamin D has a well-known role in mineral metabolism and bone health, and its supplementation in young children is well established for preventing rickets [28].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Deficiency in a Portuguese Cohort of Patients with Inflammatory Bowel Disease: Prevalence and Relation to Disease Activity

Branco

Cardoso

Anapaz

et al. 2018

GE Port J Gastroenterol

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Background and Aims: Vitamin D deficiency is more common in inflammatory bowel disease (IBD) patients than in the general population. However, there are conflicting data about predictive factors of vitamin D deficiency and its potential association with disease activity. The aims of this study were to determine the prevalence and predictive factors of vitamin D deficiency and to evaluate a possible association with disease activity. Methods: A prospective observational study was conducted, including patients with IBD from January to July 2016. The Endocrine Society guidelines were considered for defining levels of serum 25-hydroxyvitamin D (25-OH-D) as follows: deficient (< 20 ng/mL, < 10 ng/mL being severe deficiency), insufficient (21–29 ng/mL), and adequate (> 30 ng/mL). Results: A total of 152 patients (52% men; 47.2 ± 17.3 years) were included, of whom 70% had Crohn’s disease (CD). Thirty-seven percent of patients were on immunosuppressors and 17% were on biologics. The majority were outpatients (88.2%). Mean 25-OH-D levels were 17.1 ± 8 ng/mL (CD: 16.7 ± 8 ng/mL vs. ulcerative colitis: 17.6 ± 7 ng/mL, p = 0.1). Inadequate levels were present in 90.8% of patients (deficiency: 68.4%; insufficiency: 22.4%). A significant negative correlation between 25-OH-D levels and age (r = –0.2, p = 0.04), C-reactive protein (CRP) levels (r = –0.22, p = 0.004), and Harvey-Bradshaw index (HBi) (r = –0.32, p = 0.001) was found. Patients with severe deficiency showed a higher CRP (0.6 vs. 1.4 mg/dL, p = 0.03), erythrocyte sedimentation rate (ESR) (22 vs. 31 mm/h, p = 0.03), and HBi (2 vs. 5, p < 0.001) and lower hemoglobin (13.6 vs. 12.7 g/dL, p = 0.02). There was no association between vitamin D deficiency and gender, type, extent, and duration of disease, surgery, and other measures of disease activity, such as ESR, hemoglobin (these 2 items except for severe deficiency), fecal calprotectin, or Truelove and Witts classification. Conclusions: There is a high prevalence of inadequate levels of vitamin D in IBD patients, particularly deficiency (68.4%). There seems to exist an association between lower levels of vitamin D and higher disease activity, especially in CD.

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“…Vitamin D is a fat-soluble secosteroid hormone that has been attributed to immunomodulatory functions in patients with IBD [27]. High prevalence rates of vitamin D deficiency among IBD patients ranging between 22 and 63% -depending on which threshold value for serum vitamin D was used to signify deficiency -indicate its significance as an environmental factor in IBD [7,[28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

High Prevalence of Vitamin D Deficiency among Patients with Inflammatory Bowel Disease

et al. 2017

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Background: Vitamin D is a hormone with immunomodulatory properties. Vitamin D deficiency has been reported for patients with inflammatory bowel disease (IBD). In this cross-sectional study, 25-hydroxyvitamin D3 (25-OH-D3) levels in patients with IBD were compared to those in patients with irritable bowel syndrome (IBS). Methods: A total of 181 patients, 156 with IBD and 25 with IBS, were included. The influence of disease activity, inflammatory markers, physical activity, and season were assessed. Results: A total of 58.6% (n = 58) of the patients with Crohn’s disease (CD) and 44.6% (n = 25) of the patients with ulcerative colitis (UC) had a 25-OH-D3 level < 50 nmol/L. CD patients showed significantly decreased 25-OH-D3 levels compared to the IBS patients (p = 0.018), but no significant difference was found for UC patients. In a linear regression model adjusted for age, gender, and BMI, a significant inverse association of C-reactive protein (CRP) (p = 0.031) and faecal calprotectin (FC) (p = 0.025) with 25-OH-D3 levels was observed for CD patients. Seasonal variation in 25-OH-D3 levels was found in CD patients, with significantly lower values in spring than in summer (p = 0.04). Conclusion: Vitamin D deficiency was common in all IBD patients, but more pronounced in CD patients, in whom it also showed a significant inverse association with inflammatory markers such as CRP and FC.

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Role of Vitamin D in Inflammatory Bowel Disease

Cited by 46 publications

References 125 publications

Vitamin D differentially regulates colon stem cells in patient‐derived normal and tumor organoids

Vitamin D differentially regulates colon stem cells in patient‐derived normal and tumor organoids

Vitamin D Deficiency in a Portuguese Cohort of Patients with Inflammatory Bowel Disease: Prevalence and Relation to Disease Activity

High Prevalence of Vitamin D Deficiency among Patients with Inflammatory Bowel Disease

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