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The intestinal vitamin D receptor in inflammatory bowel disease: inverse correlation with inflammation but no relationship with circulating vitamin D status.

ABSTRACT: Background:The intestinal vitamin D receptor (VDR) remains poorly characterized in patients with inflammatory bowel disease (IBD). Methods:Colonoscopic biopsies and intestinal resection specimens from the terminal ileum, ascending and sigmoid colon, from patients with and without IBD, were analyzed for VDR mRNA quantification by polymerase chain reaction, and protein localization and semi-quantification by immunohistochemistry. The relationship between VDR and intestinal inflammation, serum 25(OH)D and oral vitamin D intake was elicited. Results:A total of 725 biopsies from 20 patients with Crohn's disease (CD), 15 with ulcerative colitis (UC) and 14 non-IBD controls who underwent colonoscopy were studied. VDR gene expression and protein staining intensity was similar across all three groups, and across the intestinal segments. Sigmoid colon VDR mRNA expression inversely correlated with faecal calprotectin (r = -0.64, p = 0.026) and histological score (r = -0.67, p = 0.006) in UC, and histological score (r = -0.58, p = 0.019) in patients with CD. VDR staining intensity was higher in quiescent than diseased segments. No relationship with serum 25(OH)D or oral vitamin D intake was noted. Immunohistochemical staining of 28 intestinal resection specimens from 15 patients (5 each with CD, UC and non-IBD controls) showed diffuse VDR staining in the mucosa, submucosa and circular muscle. Conclusions:VDR transcript expression and protein staining intensity are inversely related to inflammation in IBD, but unrelated to serum 25(OH)D, and similar to non-IBD controls. Strategies to upregulate intestinal VDR, potentially translating to modulation of disease activity, require investigation.

SUBMITTER: Garg M

PROVIDER: S-EPMC6348511 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The intestinal vitamin D receptor in inflammatory bowel disease: inverse correlation with inflammation but no relationship with circulating vitamin D status.

Garg Mayur M Royce Simon G SG Tikellis Chris C Shallue Claire C Sluka Pavel P Wardan Hady H Hosking Patrick P Monagle Shaun S Thomas Merlin M Lubel John S JS Gibson Peter R PR

Therapeutic advances in gastroenterology 20190118

<h4>Background</h4>The intestinal vitamin D receptor (VDR) remains poorly characterized in patients with inflammatory bowel disease (IBD).<h4>Methods</h4>Colonoscopic biopsies and intestinal resection specimens from the terminal ileum, ascending and sigmoid colon, from patients with and without IBD, were analyzed for VDR mRNA quantification by polymerase chain reaction, and protein localization and semi-quantification by immunohistochemistry. The relationship between VDR and intestinal inflammat ...[more]

PMID: 30719077

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Project description:In the course of inflammatory bowel disease (IBD) malabsorption may lead to a vitamin D deficiency and calcium-phosphate misbalance. However, the reports on the vitamin D status in children with IBD are few and ambiguous. Here, we are presenting complex analyses of multiple factors influencing 25OHD levels in IBD children (N = 62; Crohn's disease n = 34, ulcerative colitis n = 28, mean age 14.4 ± 3.01 years, F/M 23/39) and controls (n = 47, mean age 13.97 ± 2.57, F/M 23/24). Additionally, calcium-phosphate balance parameters and inflammatory markers were obtained. In children with IBD disease, activity and location were defined. Information about therapy, presence of fractures and abdominal surgery were obtained from medical records. All subjects were surveyed on the frequency and extent of exposure to sunlight (forearms, partially legs for at least 30 min a day), physical activity (at least 30 min a day) and diet (3 days diary was analyzed with the program DIETA 5). The mean 25OHD level was higher in IBD patients compared to controls (18.1 ng/mL vs. 15.5 ng/mL; p = 0.03). Only 9.7% of IBD patients and 4.25% of controls had the optimal vitamin D level (30-50 ng/mL). Despite the higher level of 25OHD, young IBD patients showed lower calcium levels in comparison to healthy controls. There was no correlation between the vitamin D level and disease activity or location of gastrointestinal tract lesions. Steroid therapy didn't have much influence on the vitamin D level while vitamin D was supplemented. Regular sun exposure was significantly more common in the control group compared to the IBD group. We found the highest concentration of vitamin D (24.55 ng/mL) with daily sun exposure. There was no significant correlation between the vitamin D level and frequency of physical activity. The analysis of dietary diaries showed low daily intake of vitamin D in both the IBD and the control group (79.63 vs. 85.14 IU/day). Pediatric patients, both IBD and healthy individuals, require regular monitoring of serum vitamin D level and its adequate supplementation.

Project description:UnlabelledIn adult inflammatory bowel disease (IBD) patients, there is a strong discrepancy between symptoms and biomarkers of inflammation. Data on pediatric IBD patients are conflicting. Therefore, we aimed to investigate the relationship between clinical symptoms and biomarkers of inflammation in pediatric IBD. Patients aged <18 years with previously diagnosed Crohn's disease (CD) or ulcerative colitis (UC) were included. Clinical disease activity was determined using the abbreviated Pediatric CD Activity Index (aPCDAI) or Pediatric UC Activity Index (PUCAI). Biochemical disease activity was assessed using fecal calprotectin (FC) and C-reactive protein (CRP). In total, 127 patients (62 male; median age 14.9 years) were included (82 CD, 45 UC). FC correlated weakly with total aPCDAI score (r s = 0.32; 95 % CI 0.12-0.51; p = 0.003) and total PUCAI score (r s = 0.36; 95 % CI 0.07-0.62; p = 0.015). Only aPCDAI components abdominal examination and perirectal disease and PUCAI component activity level had a significant correlation with levels of FC. CRP correlated weakly with total aPCDAI score (r s = 0.28; 95 % CI 0.05-0.46; p = 0.012) and aPCDAI components abdominal examination and activity level. No significant correlation was observed between CRP and total PUCAI score (r s = 0.01; 95 % CI -0.34-0.29; p = 0.961) or individual PUCAI components.ConclusionThere is a strong discrepancy between clinical symptoms and biomarkers of inflammation in children with IBD.What is known• A substantial proportion of asymptomatic pediatric inflammatory bowel disease (IBD) patients have elevated biomarkers of inflammation. • There is a strong discrepancy between symptoms and biomarkers of inflammation in adults with IBD. What is New: • Clinical symptoms are only weakly associated with levels of fecal calprotectin and serum C-reactive protein in children and adolescents with previously diagnosed IBD. • Similarly to adult IBD patients, there is a strong discrepancy between clinical symptoms and biomarkers of inflammation in children with IBD.

Dataset Information

The intestinal vitamin D receptor in inflammatory bowel disease: inverse correlation with inflammation but no relationship with circulating vitamin D status.

Publications

The intestinal vitamin D receptor in inflammatory bowel disease: inverse correlation with inflammation but no relationship with circulating vitamin D status.

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