Vitamin D deficient diet deteriorates gut barrier function by reducing α-defensins in the ileum of C57BL6J mice

Introduction  The hormone vitamin D (VD) is formed from 7-dehydrocholesterol in the skin by UV radiation. After conversion in the kidney to its active form calcitriol, VD can act on gene expression by binding to the nuclear vitamin D receptor (VDR) [1]. Besides its role for a healthy bone metabolism, VD is also known to be involved in immunomodulation and gut barrier functionality [2]. However, the underlying mechanisms through which VD affects the intestinal barrier remain unclear.

Material and Methods  To examine the impact of a VD deficient diet on the functionality and integrity of the intestinal barrier, 24 female C57BL/6J mice were fed either a diet lacking in vitamin D (VDd) or a control diet (CD) for 12 weeks respectively. Markers of antimicrobial peptide defense and regulatory pathways were assessed in ileum and colon.

Results  Feeding a VDd for 12 weeks resulted in reduced production and activity of paneth cell antimicrobial peptides in the ileum. Gene expression analysis showed decreased mRNA expression of Crp4 (p < 0.05), PanCrypt (p < 0.05) and MMP7 (p < 0.01). In contrast, several components of the Wnt signaling pathway, which regulates AMP gene expression, were unchanged (Wnt3, Wnt5a, Wnt9a (p > 0,05), TCF1 (p > 0,05) and TCF4 (p > 0,05)) in VDd-fed mice. Additionally, mRNA expression of VDR remained unchanged in these mice.

Conclusion  Our data revealed that a vitamin D deficient diet deteriorates gut barrier function and modulates immunity by reducing the production and activity of α-defensins in the ileum. As no significant changes were found for the Wnt signaling pathway and VDR, further studies are needed to investigate underlying mechanisms.

Publication History

Article published online:
26 May 2023