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.

Keywords: Crohn’s disease; inflammatory bowel disease; ulcerative colitis; vitamin D; vitamin D receptor.

Figure 1.

Colonoscopic biopsy VDR gene expression among patients with IBD and non-IBD controls in the terminal ileum, ascending colon and sigmoid colon. Expression is relative to the median of the non-IBD control terminal ileal specimens. Circles represent patients with CD, squares patients with UC and triangles non-IBD controls (NC). CD, Crohn’s disease; IBD, inflammatory bowel disease; NC, non-IBD controls; UC, ulcerative colitis; VDR, vitamin D receptor.

Figure 2.

Correlation of intestinal VDR mRNA expression with serum 25(OH)D level across all participants. Expression is relative to the median of the non-IBD control terminal ileal specimens. IBD, inflammatory bowel disease; VDR, vitamin D receptor.

Figure 3.

Relationship between intestinal VDR mRNA expression and intestinal inflammation. Relationship between VDR expression and faecal calprotectin in patients with (a) CD and (b) UC; and relationship between VDR mRNA expression and degree of histological remission in patients with (c) CD and (d) UC. Expression is relative to the median of the non-IBD control terminal ileal specimens. CD, Crohn’s disease; IBD, inflammatory bowel disease; UC, ulcerative colitis; VDR, vitamin D receptor.

Figure 4.

VDR immunohistochemical staining of mucosa of colonoscopic biopsies in inflamed and noninflamed colon. Staining is expressed as the percentage of DAB+ particle density identified at an arbitrary detection threshold using ImageJ image processing software. DAB, diaminobenzidine; VDR, vitamin D receptor.

Figure 5.

Representative immunohistochemical images of VDR in the terminal ileum, ascending colon and sigmoid colon among patients with CD, UC and non-IBD controls (a) terminal ileum; (b) ascending colon; and (c) sigmoid colon. Images represent samples with the median of the semi-quantification. CD, Crohn’s disease; IBD, inflammatory bowel disease; UC, ulcerative colitis; VDR, vitamin D receptor.