维生素D在克罗恩病中的作用机制及外源性补充作用

夏雨, 周娟, 赵红梅, 游洁玉

中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (8) : 870-876.

PDF(1080 KB)
HTML
PDF(1080 KB)
HTML
中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (8) : 870-876. DOI: 10.7499/j.issn.1008-8830.2212064
综述

维生素D在克罗恩病中的作用机制及外源性补充作用

  • 夏雨1, 周娟2, 赵红梅2, 游洁玉1,2
作者信息 +

Mechanism of action and exogenous supplementation of vitamin D in Crohn's disease

  • XIA Yu, ZHOU Juan, ZHAO Hong-Mei, YOU Jie-Yu
Author information +
文章历史 +

摘要

维生素D不仅可调节钙磷代谢,还具有免疫调节的作用。克罗恩病(Crohn's disease,CD)患者普遍缺乏维生素D。研究表明维生素D与CD等自身免疫性疾病有关,通过调节肠道免疫、修复肠黏膜屏障、抑制肠纤维化、增强对英夫利西单抗的应答、调节肠道菌群等途径改善CD患者的病情,促进患者的康复。外源性维生素D补充在提高血清维生素D水平的同时可以诱导疾病的缓解。但目前仅有少数随机双盲、安慰剂对照试验研究维生素D在CD中的治疗效果,有关维生素D最佳的补充形式、具体的补充剂量及需要维持的最佳血清浓度尚未明确。该文主要讨论维生素D在CD的作用机制及外源性维生素D补充对CD的有益作用。

Abstract

Vitamin D can not only regulate calcium and phosphorus metabolism, but also exert an immunoregulatory effect. Vitamin D deficiency is common in patients with Crohn's disease (CD). Studies have shown that vitamin D is associated with CD and other autoimmune diseases and can improve the condition of patients with CD and promote their recovery by regulating intestinal immunity, repairing the intestinal mucosal barrier, inhibiting intestinal fibrosis, enhancing the response to infliximab, and regulating intestinal microbiota. Exogenous vitamin D supplementation can induce disease remission while increasing the serum level of vitamin D. However, only a few randomized, double-blind, and placebo-controlled trials have investigated the therapeutic effect of vitamin D in CD, and the optimal form of vitamin D supplementation, the specific dosage of vitamin D supplementation, and the optimal serum maintenance concentration of vitamin D remain to be clarified. This article mainly discusses the mechanism of action of vitamin D in CD and the beneficial effect of exogenous vitamin D supplementation on CD.

关键词

克罗恩病 / 维生素D / 作用机制 / 儿童

Key words

Crohn's disease / Vitamin D / Mechanism of action / Child

引用本文

导出引用
夏雨, 周娟, 赵红梅, 游洁玉. 维生素D在克罗恩病中的作用机制及外源性补充作用[J]. 中国当代儿科杂志. 2023, 25(8): 870-876 https://doi.org/10.7499/j.issn.1008-8830.2212064
XIA Yu, ZHOU Juan, ZHAO Hong-Mei, YOU Jie-Yu. Mechanism of action and exogenous supplementation of vitamin D in Crohn's disease[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(8): 870-876 https://doi.org/10.7499/j.issn.1008-8830.2212064

参考文献

1 Plichta DR, Graham DB, Subramanian S, et al. Therapeutic opportunities in inflammatory bowel disease: mechanistic dissection of host-microbiome relationships[J]. Cell, 2019, 178(5): 1041-1056. PMID: 31442399. PMCID: PMC6778965. DOI: 10.1016/j.cell.2019.07.045.
2 中华医学会儿科学分会消化学组, 中华医学会儿科学分会临床营养学组. 儿童炎症性肠病诊断和治疗专家共识[J]. 中华儿科杂志, 2019, 57(7): 501-507. PMID: 31269548. DOI: 10.3760/cma.j.issn.0578‐1310.2019.07.002.
3 Raftery T, O'Sullivan M. Optimal vitamin D levels in Crohn's disease: a review[J]. Proc Nutr Soc, 2015, 74(1): 56-66. PMID: 25497215. DOI: 10.1017/S0029665114001591.
4 纪联君, 李星. 维生素D缺乏症患儿的炎症性肠病的研究[J]. 中国妇幼健康研究, 2019, 30(5): 654-656. DOI: 10.3969/j.issn.1673-5293.2019.05.030.
5 Alkhouri RH, Hashmi H, Baker RD, et al. Vitamin and mineral status in patients with inflammatory bowel disease[J]. J Pediatr Gastroenterol Nutr, 2013, 56(1): 89-92. PMID: 22832510. DOI: 10.1097/MPG.0b013e31826a105d.
6 Fabisiak N, Fabisiak A, Watala C, et al. Fat-soluble vitamin deficiencies and inflammatory bowel disease: systematic review and meta-analysis[J]. J Clin Gastroenterol, 2017, 51(10): 878-889. PMID: 28858940. DOI: 10.1097/MCG.0000000000000911.
7 Yamada A, Komaki Y, Komaki F, et al. The correlation between vitamin D levels and the risk of postoperative recurrence in Crohn's disease[J]. Digestion, 2021, 102(5): 767-775. PMID: 33556932. DOI: 10.1159/000513589.
8 López-Mu?oz P, Beltrán B, Sáez-González E, et al. Influence of vitamin D deficiency on inflammatory markers and clinical disease activity in IBD patients[J]. Nutrients, 2019, 11(5): 1059. PMID: 31083541. PMCID: PMC6567866. DOI: 10.3390/nu11051059.
9 Zhao J, Wang Y, Gu Q, et al. The association between serum vitamin D and inflammatory bowel disease[J]. Medicine (Baltimore), 2019, 98(18): e15233. PMID: 31045762. PMCID: PMC6504311. DOI: 10.1097/MD.0000000000015233.
10 杨莉丽, 江丹玲, 陈文科, 等. 克罗恩病患者血清总25羟维生素D及细胞因子水平表达与疾病活动指数的相关性研究[J]. 现代检验医学杂志, 2022, 37(1): 195-198. DOI: 10.3969/j.issn.1671-7414.2022.01.040.
11 苏鹏, 付杰, 刘萍, 等. 25-羟维生素D联合TNF-α对克罗恩病的辅助诊断价值分析[J]. 标记免疫分析与临床, 2020, 27(5): 799-804. DOI: 10.11748/bjmy.issn.1006-1703.2020.05.019.
12 陈丹, 李骥, 张鑫垚, 等. 克罗恩病患者维生素D水平与细胞因子的相关性研究[J]. 中华医学杂志, 2020, 100(10): 757-762. PMID: 32192288. DOI: 10.3760/cma.j.cn112137-20190917-02050.
13 刘利九, 李宇宁, 凌继祖. 儿童维生素D营养状况及临床相关疾病研究进展[J]. 中国现代医药杂志, 2018, 20(7): 101-105. DOI: 10.3969/j.issn.1672-9463.2018.07.032.
14 Janssen CE, Globig AM, Busse Grawitz A, et al. Seasonal variability of vitamin D status in patients with inflammatory bowel disease: a retrospective cohort study[J]. PLoS One, 2019, 14(5): e0217238. PMID: 31120977. PMCID: PMC6532907. DOI: 10.1371/journal.pone.0217238.
15 Horta G, Soto S, Labarca G. Vitamin D levels in patients with inflammatory bowel disease[J]. Rev Med Chil, 2021, 149(3): 393-398. PMID: 34479318. DOI: 10.4067/s0034-98872021000300393.
16 罗优优, 陈洁. 儿童克罗恩病维生素D缺乏状况及其危险因素研究[J]. 中华儿科杂志, 2015, 53(7): 516-521. PMID: 26310644. DOI: 10.3760/cma.j.issn.0578-1310.2015.07.010.
17 Borrelli O, Bascietto C, Viola F, et al. Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn's disease[J]. Dig Liver Dis, 2004, 36(5): 342-347. PMID: 15191204. DOI: 10.1016/j.dld.2003.12.014.
18 Hizarcioglu-Gulsen H, Kaplan JL, Moran CJ, et al. The impact of vitamin D on response to anti-tumor necrosis factor-α therapy in children with inflammatory bowel disease[J]. J Pediatr Gastroenterol Nutr, 2021, 72(5): e125-e131. PMID: 33847289. DOI: 10.1097/MPG.0000000000003064.
19 Valvano M, Magistroni M, Mancusi A, et al. The usefulness of serum vitamin D levels in the assessment of IBD activity and response to biologics[J]. Nutrients, 2021, 13(2): 323. PMID: 33499406. PMCID: PMC7910959. DOI: 10.3390/nu13020323.
20 程艳春. 血浆25(OH)D与谷胱甘肽过氧化物酶在评估克罗恩病患儿基本活动度的应用价值[J]. 现代消化及介入诊疗, 2019, 24(11): 1296-1299. DOI: 10.3969/j.issn.1672-2159.2019.11.018.
21 Xia SL, Min QJ, Shao XX, et al. Influence of vitamin D3 supplementation on infliximab effectiveness in Chinese patients with Crohn's disease: a retrospective cohort study[J]. Front Nutr, 2021, 8: 739285. PMID: 34746207. PMCID: PMC8568764. DOI: 10.3389/fnut.2021.739285.
22 Ham NS, Hwang SW, Oh EH, et al. Influence of severe vitamin D deficiency on the clinical course of inflammatory bowel disease[J]. Dig Dis Sci, 2021, 66(2): 587-596. PMID: 32219610. DOI: 10.1007/s10620-020-06207-4.
23 Nielsen OH, Rejnmark L, Moss AC. Role of vitamin D in the natural history of inflammatory bowel disease[J]. J Crohns Colitis, 2018, 12(6): 742-752. PMID: 29529167. DOI: 10.1093/ecco-jcc/jjy025.
24 Zundler S, Becker E, Schulze LL, et al. Immune cell trafficking and retention in inflammatory bowel disease: mechanistic insights and therapeutic advances[J]. Gut, 2019, 68(9): 1688-1700. PMID: 31127023. DOI: 10.1136/gutjnl-2018-317977.
25 庞园园, 方莹, 周影. 维生素 D 与炎症性肠病的相关性研究进展[J]. 新医学, 2015, 46(6): 341-345. DOI: 10.3969/g.issn.0253-9802.2015.06.001.
26 Guan Y, Hao Y, Guan Y, et al. Effects of vitamin D supplementation on blood markers in ulcerative colitis patients: a systematic review and meta-analysis[J]. Eur J Nutr, 2022, 61(1): 23-35. PMID: 34075433. DOI: 10.1007/s00394-021-02603-2.
27 Gubatan J, Moss AC. Vitamin D in inflammatory bowel disease: more than just a supplement[J]. Curr Opin Gastroenterol, 2018, 34(4): 217-225. PMID: 29762159. DOI: 10.1097/MOG.0000000000000449.
28 Gisbert-Ferrándiz L, Cosín-Roger J, Hernández C, et al. Diminished vitamin D receptor protein levels in Crohn's disease fibroblasts: effects of vitamin D[J]. Nutrients, 2020, 12(4): 973. PMID: 32244667. PMCID: PMC7230839. DOI: 10.3390/nu12040973.
29 Li YC, Chen Y, Du J. Critical roles of intestinal epithelial vitamin D receptor signaling in controlling gut mucosal inflammation[J]. J Steroid Biochem Mol Biol, 2015, 148: 179-183. PMID: 25603468. PMCID: PMC4361385. DOI: 10.1016/j.jsbmb.2015.01.011.
30 苏丽坦古丽·麦合木提, 周辛欣, 季峰. 维生素D及其受体在炎症性肠病相关肠纤维化中的作用研究进展[J]. 浙江医学, 2021, 43(1): 102-106. DOI: 10.12056/j.issn.1006-2785.2021.43.1.2020-4208.
31 Murdaca G, Gerosa A, Paladin F, et al. Vitamin D and microbiota: is there a link with allergies?[J]. Int J Mol Sci, 2021, 22(8): 4288. PMID: 33924232. PMCID: PMC8074777. DOI: 10.3390/ijms22084288.
32 Battistini C, Ballan R, Herkenhoff ME, et al. Vitamin D modulates intestinal microbiota in inflammatory bowel diseases[J]. Int J Mol Sci, 2020, 22(1): 362. PMID: 33396382. PMCID: PMC7795229. DOI: 10.3390/ijms22010362.
33 杨宏, 张铭光, 王治东, 等. 血清免疫炎症相关蛋白复合物、25-羟维生素D、脂肪细胞因子与炎症性肠病患者疾病活动性和肠道菌群的相关性研究[J]. 现代生物医学进展, 2022, 22(14): 2653-2657. DOI: 10.13241/j.cnki.pmb.2022.14.010.
34 Basson A. Vitamin D and Crohn's disease in the adult patient: a review[J]. JPEN J Parenter Enteral Nutr, 2014, 38(4): 438-458. PMID: 24154811. DOI: 10.1177/0148607113506013.
35 Del Pinto R, Pietropaoli D, Chandar AK, et al. Association between inflammatory bowel disease and vitamin D deficiency: a systematic review and meta-analysis[J]. Inflamm Bowel Dis, 2015, 21(11): 2708-2717. PMID: 26348447. PMCID: PMC4615394. DOI: 10.1097/MIB.0000000000000546.
36 Shirwaikar Thomas A, Criss ZK, Shroyer NF, et al. Vitamin D receptor gene single nucleotide polymorphisms and association with vitamin D levels and endoscopic disease activity in inflammatory bowel disease patients: a pilot study[J]. Inflamm Bowel Dis, 2021, 27(8): 1263-1269. PMID: 33165606. PMCID: PMC8785942. DOI: 10.1093/ibd/izaa292.
37 Narula N, Cooray M, Anglin R, et al. Impact of high-dose vitamin D3 supplementation in patients with Crohn's disease in remission: a pilot randomized double-blind controlled study[J]. Dig Dis Sci, 2017, 62(2): 448-455. PMID: 27975236. DOI: 10.1007/s10620-016-4396-7.
38 Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary reference intakes for calcium and vitamin D[M]. Washington (DC): National Academies Press (US), 2011: 363.
39 J?rgensen SP, Agnholt J, Glerup H, et al. Clinical trial: vitamin D3 treatment in Crohn's disease: a randomized double-blind placebo-controlled study[J]. Aliment Pharmacol Ther, 2010, 32(3): 377-383. PMID: 20491740. DOI: 10.1111/j.1365-2036.2010.04355.x.
40 Yang L, Weaver V, Smith JP, et al. Therapeutic effect of vitamin d supplementation in a pilot study of Crohn's patients[J]. Clin Transl Gastroenterol, 2013, 4(4): e33. PMID: 23594800. PMCID: PMC3636524. DOI: 10.1038/ctg.2013.1.
41 Bendix M, Dige A, J?rgensen SP, et al. Seven weeks of high-dose vitamin D treatment reduces the need for infliximab dose-escalation and decreases inflammatory markers in Crohn's disease during one-year follow-up[J]. Nutrients, 2021, 13(4): 1083. PMID: 33810258. PMCID: PMC8065492. DOI: 10.3390/nu13041083.
42 Bafutto M, Oliveira EC, Rezende Filho J. Use of vitamin D with anti-tumor necrosis factor therapy for Crohn's disease[J]. Gastroenterology Res, 2020, 13(3): 101-106. PMID: 32655726. PMCID: PMC7331853. DOI: 10.14740/gr1264.
43 Simek RZ, Prince J, Syed S, et al. Pilot study evaluating efficacy of 2 regimens for hypovitaminosis D repletion in pediatric inflammatory bowel disease[J]. J Pediatr Gastroenterol Nutr, 2016, 62(2): 252-258. PMID: 26196201. PMCID: PMC4863642. DOI: 10.1097/MPG.0000000000000915.
44 ?ledzińska K, Landowski P, ?mijewski MA, et al. Diet, sun, physical activity and vitamin D status in children with inflammatory bowel disease[J]. Nutrients, 2022, 14(5): 1029. PMID: 35268001. PMCID: PMC8912613. DOI: 10.3390/nu14051029.
45 Ananthakrishnan AN, Cagan A, Gainer VS, et al. Normalization of plasma 25-hydroxy vitamin D is associated with reduced risk of surgery in Crohn's disease[J]. Inflamm Bowel Dis, 2013, 19(9): 1921-1927. PMID: 23751398. PMCID: PMC3720838. DOI: 10.1097/MIB.0b013e3182902ad9.
46 Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline[J]. J Clin Endocrinol Metab, 2011, 96(7): 1911-1930. PMID: 21646368. DOI: 10.1210/jc.2011-0385.
47 林子闻. 血清维生素D水平与克罗恩病活动度的关系[D]. 杭州: 浙江大学, 2017.
48 徐小红, 方声, 包丹妮. 克罗恩病患儿血清维生素D含量及其与机体免疫状态、全身炎症反应程度的相关分析[J]. 实用预防医学, 2021, 28(1): 106-108. DOI: 10.3969/j.issn.1006-3110.2021.01.029.
49 Parizadeh SM, Jafarzadeh-Esfehani R, Hassanian SM, et al. Vitamin D in inflammatory bowel disease: from biology to clinical implications[J]. Complement Ther Med, 2019, 47: 102189. PMID: 31779998. DOI: 10.1016/j.ctim.2019.08.023.

基金

湖南省儿童医院临床研究(转化)中心资助项目(2022CR09)。

PDF(1080 KB)
HTML

Accesses

Citation

Detail

段落导航
相关文章

/