Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis.
Vitamin D exerts anti-inflammatory actions both in vitro and in murine models of colitis. In previous studies, we demonstrated that vitamin D protects against the development of colitis by maintaining the integrity of the intestinal mucosal barrier.



We sought to evaluate whether deficient serum 25 hydroxyvitamin D [25(OH)D] concentrations are associated with increased mucosal inflammation, a loss of epithelial junctional proteins, and an increase in mucosal inflammatory cytokines in patients with ulcerative colitis (UC).



We prospectively enrolled 230 subjects with UC. Serum 25(OH)D concentrations were compared with the Mayo endoscopic score, the total Mayo score, and histologic activity. Colonic mucosal expression concentrations of vitamin D receptor (VDR), E-cadherin, zonula occluden 1 (ZO-1), occludin, claudin-2, tumor necrosis factor α (TNF-α), and interleukin 8 (IL-8) were compared between dichotomous groups with low or high serum 25(OH)D concentrations.



The mean serum 25(OH)D concentration was 21.8 ng/mL. Subjects stratified by concentrations included 12.6% ≥30 ng/mL, 45.6% ≥20 to <30 ng/mL, 37.4% ≥10 to <20 ng/mL, and 4.4% <10 ng/mL. There was an inverse association between serum 25(OH)D concentrations and mucosal inflammation as assessed by the Mayo endoscopy score (P = 0.01), disease activity as indicated by the total Mayo score (P = 0.001), and histologic activity (P = 0.02). A serum 25(OH)D concentration <20 ng/mL was associated with decreased mucosal transcript and protein expression concentrations of VDR, E-cadherin, and occludin as well as decreased protein expression of ZO-1, whereas TNF-α and IL-8 mucosal transcript expression concentrations were increased.



In UC patients, serum 25(OH)D concentration is inversely correlated with mucosal inflammation and disease activity. These results, coupled with the findings that serum 25(OH)D concentrations correlate with the mucosal expression of VDR as well as epithelial junction proteins and inversely with proinflammatory cytokines, suggest that vitamin D deficiency may contribute to UC inflammation by disrupting epithelial barrier function.
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and.
Katherine
K
Meckel
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and.
Yan Chun
YC
Li
Section of Gastroenterology, Hepatology, and Nutrition.
John
J
Lim
Departments of Health Sciences and.
Masha
M
Kocherginsky
Inflammatory Bowel Disease Center, and Pathology, University of Chicago Medicine, Chicago, IL;
Chris
C
Weber
Section of Gastroenterology, Hepatology, and Nutrition.
Anas
A
Almoghrabi
Section of Gastroenterology, Hepatology, and Nutrition.
Xindi
X
Chen
Section of Gastroenterology, Hepatology, and Nutrition.
Austin
A
Kaboff
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and.
Farhana
F
Sadiq
Digestive Diseases Center, Northwestern University, Chicago, IL; and.
Stephen B
SB
Hanauer
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and.
Russell D
RD
Cohen
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and.
John
J
Kwon
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and.
David T
DT
Rubin
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and.
Ira
I
Hanan
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and.
Atsushi
A
Sakuraba
Section of Gastroenterology, Northshore University, Evanston, IL.
Eugene
E
Yen
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and.
Marc
M
Bissonnette
Section of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, and jpekow@medicine.bsd.uchicago.edu.
Joel
J
Pekow
D000328:Adult; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D062793:Occludin / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D016209:Interleukin-8; D062793:Occludin; D018167:Receptors, Calcitriol; C569042:TJP1 protein, human; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D
inflammatory bowel disease; mucosal inflammation; tight junction; ulcerative colitis; vitamin D