Low Sun Exposure and Vitamin D Deficiency as Risk Factors for Inflammatory Bowel Disease, With a Focus on Childhood Onset

Holmes, Elizabeth A.; Harris, Rachael; Lucas, Robyn

doi:10.1111/php.13007

Cited by 16 publications

(17 citation statements)

References 105 publications

(135 reference statements)

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“…There is now recognition that UV irradiation of the skin (and possibly the eyes) has profound effects on systemic immunity (16). The overall effect is very similar to that associated with vitamin D—upregulation of innate immunity and suppression of adaptive immunity, particularly Th1 and Th17 (pro-inflammatory) pathways, and upregulation of T-regulatory and B-regulatory cells (17), and modulation of the microbiome [reviewed in (4)]. Our results suggest that recent sun exposure, or perhaps cumulative exposure over several years, is of particular importance.…”

Section: Discussionsupporting

confidence: 65%

Higher Sun Exposure is Associated With Lower Risk of Pediatric Inflammatory Bowel Disease

Holmes

Ponsonby

Pezic

et al. 2019

J. pediatr. gastroenterol. nutr.

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Objectives:The incidence of pediatric inflammatory bowel disease (IBD) is increasing worldwide. Ecological studies show higher incidence in regions at higher latitude or lower ambient ultraviolet radiation; individual-level associations with sun exposure have not been assessed.Methods:We recruited children (0–17 years) with IBD from 2 large hospitals in Melbourne, Australia. Control participants were recruited from the day surgery unit of one of the same hospitals. Questionnaires provided data on demographics, past sun exposure, the likelihood of sunburn (skin sensitivity) or tanning following sun exposure, use of sun protection, physical activity, and parental smoking and education. Grandparent ancestry was used to determine participant ethnicity. Cases and controls were matched on age and sex. We used conditional logistic regression to test the association between being an IBD case and past sun exposure at different ages, adjusted for a range of other factors.Results:After matching, n = 99 cases and n = 396 controls were included in the analysis. In multivariable analysis, for each 10 min increment in leisure-time sun exposure in summer or winter there was a linear 6% reduction in the odds of having IBD (P = 0.002). Results were similar in sensitivity analyses including only the most recently diagnosed cases, only Caucasian cases and controls, only those with symptom onset within the year before study entry, or additionally adjusted for age or physical activity.Conclusions:Higher sun exposure in the previous summer or winter was associated with a reduced risk of having IBD. There are plausible pathways that could mediate this effect.

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Section: Discussionsupporting

confidence: 65%

Higher Sun Exposure is Associated With Lower Risk of Pediatric Inflammatory Bowel Disease

Holmes

Ponsonby

Pezic

et al. 2019

J. pediatr. gastroenterol. nutr.

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“…Previous studies reported diminished VDR levels in intestinal biopsies from patients with inflammatory bowel disease [25], and our results extend these observations by showing for the first time that fibroblasts obtained from the damaged intestine of CD patients present lower VDR protein levels than those obtained from the non-damaged tissue of the same patient. Serum VD levels were correlated with colonic VDR expression in normal mucosa [26], and these levels seem to be dependent on several factors, such as body mass index [27] or sun exposure [28]. However, the difference in VDR protein levels detected in the present study between samples of the same patient, excludes genetics or changes in serum VD levels as responsible for the VDR down-regulation observed in cells coming from damaged tissues.…”

Section: Discussionmentioning

confidence: 47%

Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D

et al. 2020

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Vitamin D (VD) deficiency has been associated to Crohn’s disease (CD) pathogenesis, and the exogenous administration of VD improves the course of the disease, but the mechanistic basis of these observations remains unknown. Vitamin D receptor (VDR) mediates most of the biological functions of this hormone, and we aim to analyze here the expression of VDR in intestinal tissue, epithelial cells, and fibroblasts from CD patients. The effects of VD on a fibroblast wound healing assay and murine intestinal fibrosis are also analyzed. Our data show diminished VDR protein levels in surgical resections and epithelial cells from CD patients. In intestinal fibroblasts isolated from damaged tissue of CD patients, we detected enhanced migration and decreased VDR expression compared with both fibroblasts from non-damaged tissue of the same CD patient or control fibroblasts. Treatment with VD increased VDR protein levels, avoided the accelerated migration in CD fibroblasts, and prevented murine intestinal fibrosis induced by the heterotopic transplant model. In conclusion, our study demonstrates diminished VDR protein levels associated with enhanced migration in intestinal fibroblasts from damaged tissue of CD patients. In these cells, VD accumulates VDR and normalizes migration, which supports that CD patients would benefit from the VD anti-fibrotic therapeutic value that we demonstrate in a murine experimental model.

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“…Evidence for the effect of vitamin D on immune tolerance comes from reported negative correlations between vitamin D status and a number of autoimmune and inflammatory diseases like diabetes mellitus type I, Hashimoto thyroiditis, inflammatory bowel diseases, and multiple sclerosis among others. This relationship is supported by the common observation of a North-South gradient in the prevalence of these diseases, suggesting a role for the low UV sunlight intensity and hence lower endogenous synthesis of vitamin D at higher latitudes [ 81 - 83 ].…”

Section: Vitamin Dmentioning

confidence: 66%

The Role of the Status of Selected Micronutrients in Shaping the Immune Function

Elmadfa

Meyer

2019

EMIDDT

106

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Objective: This narrative review gives an overview on the essential role of adequate nutrition to an optimally functioning immune defence. Micronutrients act as regulators of the immune response, with the focus of this review on the immunomodulatory effects of the trace elements iron, zinc and selenium, and the vitamins A, D, E, C, B6 and B12 and folic acid. Results: Iron deficiency especially impairs the Th1 cell-borne cellular immunity. T lymphocytes are also most affected by a deficiency of zinc, needed for their maturation and the balance between the different T cell subpopulations and acting as a redox signal in the regulation of many enzymes. Selenium is also involved in redox reactions as the glutathione peroxidases and other redox enzymes are selenoproteins. Selenium status has shown special effects on cellular immunity and resistance to viral infections. : Vitamin A in the form of retinoic acid induces a humoral Th2 cell response via antigen-presenting cells and is involved in maintaining intestinal immune defence and tolerance through its nuclear receptor RAR and via kinase signalling cascades. Immune tolerance is particularly promoted by vitamin D acting through dendritic cells to stimulate the differentiation of regulatory T cells. Vitamin E has antiinflammatory effects and stimulates naïve T cells especially in the elderly. Besides its antioxidative properties, vitamin C has effects on cell signalling and epigenetic regulation. The B vitamins are required for cytotoxic cellular immunity and modulateT cell responses. : A diverse diet and regular exposure to sunlight are the best sources for a balanced nutrient supply to maintain an optimal immune defence.

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Low Sun Exposure and Vitamin D Deficiency as Risk Factors for Inflammatory Bowel Disease, With a Focus on Childhood Onset

Cited by 16 publications

References 105 publications

Higher Sun Exposure is Associated With Lower Risk of Pediatric Inflammatory Bowel Disease

Higher Sun Exposure is Associated With Lower Risk of Pediatric Inflammatory Bowel Disease

Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D

The Role of the Status of Selected Micronutrients in Shaping the Immune Function

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