Dutch Crohn’s disease patients are not at increased risk for vitamin A or D deficiency.

Wymenga, L.F. (2014) Dutch Crohn’s disease patients are not at increased risk for vitamin A or D deficiency. thesis, Medicine.

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Abstract

Background and aims: Crohn’s disease (CD) is characterized by chronic inflammation of the digestive tract, typically involving the terminal ileum, the site where bile acid reabsorption takes place. As a consequence, many CD patients suffer from bile acid malabsorption and are at risk for deficiency of fat-soluble vitamins, including A and D. These vitamins have critical roles in controlling inflammation, e.g. the vitamin A-metabolite retinoic acid induces FoxP3+ regulatory T cells that suppress inflammation. Here, we assessed the occurrence of vitamin A and/or D deficiency in CD patients and investigated whether ileocecal resection and/or inflammation affects ileal expression of FoxP3, the vitamin A-metabolizing enzyme RALDH-2 and bile acid transporters. Moreover, we analyzed whether vitamin A-deficiency directly affects FoxP3 expression in rat ileum. Methods: Serum vitamin A and D levels were measured in 86 CD patients with and 74 CD patients without ileocecal resection. Vitamin A levels <0.7 umol/L and vitamin D levels <50 umol/L were considered deficient. qRT-PCR analysis was performed on ileal biopsies of CD patients with ileocecal resection and healthy controls to determine the expression of FoxP3, RALDH-2, ASBT, IBABP, OST-α and OST-β. Ileal expression of FoxP3 was analyzed in vitamin A- or placebo-treated vitamin A deficient (VAD) and sufficient (VAS) rats. Results: All 160 CD patients showed serum vitamin A levels of >0.7 umol/L. The number of vitamin D deficient patients was comparable between the groups with or without ileocecal resection (39.5% vs. 48.7%, respectively). FoxP3 expression was significantly higher in inflamed ileal patient tissue. RALDH-2 expression was significantly increased CD patient tissue, both in non-inflamed ileum, compared to controls. No significant difference in ASBT expression was observed. Expression of IBABP, OST-α and OST-β was significantly higher in non-inflamed ileal tissue of CD patients. Ileum from VAD and VAS rats showed similar FoxP3 expression. Conclusions: CD patients are not at risk for vitamin A deficiency, while the frequency of vitamin D deficiency is not higher than in the general population. Generation of FoxP3+ regulatory T cells is not impaired in CD patients with ileocecal resection, while these patients show a compensatory induction of bile acid transporters in the non-inflamed ileal tissue.

Item Type:	Thesis (Thesis)
Supervisor name:	Faber, Prof. Dr. K.N. and Dijkstra, Prof. Dr. G. and Blokzijl, T.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:52
Last Modified:	25 Jun 2020 10:52
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1333

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