Maternal Vitamin D Deficiency Increases Intestinal Permeability and Programs Wnt/ß-Catenin Pathway in BALB/C Mice.

BACKGROUND: Recent studies suggest that vitamin D deficiency is associated with intestinal dysfunctions, but the underlying mechanism remains unclear. This study aimed to investigate whether maternal vitamin D deficiency increases intestinal permeability in offspring and its related mechanism. METHODS: Timed-pregnant mice were fed with either a standard chow diet (SC) or a vitamin D-deprived chow diet (VD-) 6 weeks prior to breeding and kept on the same diet until the end of gestation. All offspring were fed an SC for 3 weeks after weaning and then observed for effects associated with maternal vitamin D deficiency. RESULTS: Maternal vitamin D deficiency increased intestinal permeability in offspring, which corresponded with the decreased expression of the tight junction protein claudin-1. Maternal vitamin D deficiency also repressed the messenger RNA expression of wingless/integrated family member 3a (Wnt3a) and the protein expression of nuclear ß-catenin. The decreased Wnt3a gene expression in male was concurrent with the changes in histone H4 acetylation at either promoter or coding regions. The activation of the Wnt/ß-catenin pathway protected against the impairment of intestinal permeability induced by maternal vitamin D deficiency. CONCLUSIONS: Maternal vitamin D deficiency increased intestinal permeability and decreased tight junction protein expression in offspring. The suppression of the Wnt/ß-catenin signaling pathway through histone modification might be involved in the underlying mechanism.

Bipolar disorder in youth is associated with increased levels of vitamin D-binding protein.

Genetic, dietary, and inflammatory factors contribute to the etiology of major mood disorders (MMD), thus impeding the identification of specific biomarkers to assist in diagnosis and treatment. We tested association of vitamin D and inflammatory markers in 36 adolescents with bipolar disorder (BD) and major depressive disorder (MDD) forms of MMD and without MMD (non-mood control). We also assessed the overall level of inflammation using a cell-based reporter assay for nuclear factor kappa-B (NFκB) activation and measuring antibodies to oxidized LDL. We found that these factors were similar between non-mood and MMD youth. To identify potential biomarkers, we developed a screening immunoprecipitation-sequencing approach based on inflammatory brain glia maturation factor beta (GMFß). We discovered that a homolog of GMFß in human plasma is vitamin D-binding protein (DBP) and validated this finding using immunoprecipitation with anti-DBP antibodies and mass spectrometry/sequencing analysis. We quantified DBP levels in participants by western blot. DBP levels in BD participants were significantly higher (136%) than in participants without MMD (100%). The increase in DBP levels in MDD participants (121.1%) was not statistically different from these groups. The DBP responds early to cellular damage by binding of structural proteins and activating inflammatory cells. A product of enzymatic cleavage of DBP has been described as macrophage-activating factor. Circulating DBP is comprised of heterogenous high and low molecular fractions that are only partially recognized by mono- and polyclonal ELISA and are not suitable for the quantitative comparison of DBP in non-mood and MDD participants. Our data suggest DBP as a marker candidate of BD warranting its validation in a larger cohort of adolescent and adult MMD patients.