Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis

Katherine Meckel, Yan Chun Li, John Lim, Masha Kocherginsky, Chris Weber, Anas Almoghrabi, Xindi Chen, Austin Kaboff, Farhana Sadiq, Stephen B. Hanauer, Russell D. Cohen, John Kwon, David T. Rubin, Ira Hanan, Atsushi Sakuraba, Eugene Yen, Marc Bissonnette, Joel Pekow

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Background: 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. Objective: 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). Design: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)113-120
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Volume104
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

Ulcerative Colitis
Inflammation
Serum
Calcitriol Receptors
Occludin
25-hydroxyvitamin D
Cadherins
Colitis
Interleukin-8
Vitamin D
Claudin-2
Zonula Occludens-1 Protein
Cytokines
Proteins
Vitamin D Deficiency
Tight Junctions
Endoscopy
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha

Keywords

  • Inflammatory bowel disease
  • Mucosal inflammation
  • Tight junction
  • Ulcerative colitis
  • Vitamin D

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis. / Meckel, Katherine; Li, Yan Chun; Lim, John; Kocherginsky, Masha; Weber, Chris; Almoghrabi, Anas; Chen, Xindi; Kaboff, Austin; Sadiq, Farhana; Hanauer, Stephen B.; Cohen, Russell D.; Kwon, John; Rubin, David T.; Hanan, Ira; Sakuraba, Atsushi; Yen, Eugene; Bissonnette, Marc; Pekow, Joel.

In: American Journal of Clinical Nutrition, Vol. 104, No. 1, 01.07.2016, p. 113-120.

Research output: Contribution to journalArticle

Meckel, K, Li, YC, Lim, J, Kocherginsky, M, Weber, C, Almoghrabi, A, Chen, X, Kaboff, A, Sadiq, F, Hanauer, SB, Cohen, RD, Kwon, J, Rubin, DT, Hanan, I, Sakuraba, A, Yen, E, Bissonnette, M & Pekow, J 2016, 'Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis', American Journal of Clinical Nutrition, vol. 104, no. 1, pp. 113-120. https://doi.org/10.3945/ajcn.115.123786
Meckel, Katherine ; Li, Yan Chun ; Lim, John ; Kocherginsky, Masha ; Weber, Chris ; Almoghrabi, Anas ; Chen, Xindi ; Kaboff, Austin ; Sadiq, Farhana ; Hanauer, Stephen B. ; Cohen, Russell D. ; Kwon, John ; Rubin, David T. ; Hanan, Ira ; Sakuraba, Atsushi ; Yen, Eugene ; Bissonnette, Marc ; Pekow, Joel. / Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis. In: American Journal of Clinical Nutrition. 2016 ; Vol. 104, No. 1. pp. 113-120.
@article{49b92cbba043482697ba9717784fe6b1,
title = "Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis",
abstract = "Background: 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. Objective: 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). Design: 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. Results: 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. Conclusions: 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.",
keywords = "Inflammatory bowel disease, Mucosal inflammation, Tight junction, Ulcerative colitis, Vitamin D",
author = "Katherine Meckel and Li, {Yan Chun} and John Lim and Masha Kocherginsky and Chris Weber and Anas Almoghrabi and Xindi Chen and Austin Kaboff and Farhana Sadiq and Hanauer, {Stephen B.} and Cohen, {Russell D.} and John Kwon and Rubin, {David T.} and Ira Hanan and Atsushi Sakuraba and Eugene Yen and Marc Bissonnette and Joel Pekow",
year = "2016",
month = "7",
day = "1",
doi = "10.3945/ajcn.115.123786",
language = "English (US)",
volume = "104",
pages = "113--120",
journal = "American Journal of Clinical Nutrition",
issn = "0002-9165",
publisher = "American Society for Nutrition",
number = "1",

}

TY - JOUR

T1 - Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis

AU - Meckel, Katherine

AU - Li, Yan Chun

AU - Lim, John

AU - Kocherginsky, Masha

AU - Weber, Chris

AU - Almoghrabi, Anas

AU - Chen, Xindi

AU - Kaboff, Austin

AU - Sadiq, Farhana

AU - Hanauer, Stephen B.

AU - Cohen, Russell D.

AU - Kwon, John

AU - Rubin, David T.

AU - Hanan, Ira

AU - Sakuraba, Atsushi

AU - Yen, Eugene

AU - Bissonnette, Marc

AU - Pekow, Joel

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Background: 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. Objective: 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). Design: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Objective: 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). Design: 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. Results: 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. Conclusions: 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.

KW - Inflammatory bowel disease

KW - Mucosal inflammation

KW - Tight junction

KW - Ulcerative colitis

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=84977111320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977111320&partnerID=8YFLogxK

U2 - 10.3945/ajcn.115.123786

DO - 10.3945/ajcn.115.123786

M3 - Article

VL - 104

SP - 113

EP - 120

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 1

ER -