Supplementation of Vitamin D3 and Fructooligosaccharides Downregulates Intestinal Defensins and Reduces the Species Abundance of Romboutsia ilealis in C57BL/6J Mice.

The activation of the vitamin D receptor (VDR) in the ileum has been shown to regulate Paneth cell-specific defensins, a large family of antimicrobial peptides; hence, this may serve as a potential mechanism to maintain intestinal homeostasis. Previously, we have demonstrated that a combination of vitamin D3 (VD) and fructooligosaccharides (FOSs) upregulates colonic Vdr in mice. Here, we aim to examine the effect of VD, alone or in combination with FOSs, on intestinal barrier integrity and the secretion of antimicrobial peptides, as well as the gut microbial community. Male and female C57BL/6J mice at 6 weeks old were randomized into three groups to receive the following dietary regimens (n = 10/sex/group) for 8 weeks: (1) standard AIN-93G control diet (CTR), (2) CTR + 5000 IU vitamin D3 (VD), and (3) VD + 5% fructooligosaccharides (VF). VD and VF differentially regulated the mRNA expressions of tight junction proteins in the colon and ileum. VF suppressed the upregulation of colonic ZO-1 and occludin, which was induced by VD supplementation alone. In the ileum, occludin but not ZO-1 was upregulated 20-fold in the VF-treated mice. While VD did not alter the mRNA expressions of Vdr and defensins in the ileum, these targets were downregulated by VF. Microbial analysis further reveals a shift of microbial beta diversity and a reduction in Romboutsia ilealis, a pathobiont, in VF-treated mice. Though the implications of these phenotypical and microbial changes remain to be determined, the administration of FOSs in the presence of VD may serve as an effective dietary intervention for maintaining intestinal homeostasis.

Combination of vitamin D3 and fructooligosaccharides upregulates colonic vitamin D receptor in C57BL/6J mice and affects anxiety-related behavior in a sex-specific manner.

Depression and anxiety disorders are among the most common mental health disorders that affect US adults today, frequently related to vitamin D (VD) insufficiency. Along with VD, growing evidence suggests gut microbiota likely play a role in neuropsychiatric disorders. Here, we investigated if modulation of gut microbiota would disrupt host VD status and promote behaviors related to depression and anxiety in adult mice. Six-week-old male and female C57BL/6J mice (n = 10/mice/group) were randomly assigned to receive (1) control diet (CTR), control diet treated with antibiotics (AB), control diet with total 5000 IU of VD (VD), VD treated with antibiotics (VD + AB), VD supplemented with 5% w/w fructooligosaccharides (FOS; VF), and VF diet treated with antibiotics (VF + AB), respectively, for 8 weeks. Our study demonstrated that VD status was not affected by antibiotic regimen. VD alone ameliorates anxiety-related behavior in female mice, and that combination with FOS (i.e., VF) did not further improve the outcome. Male mice, in contrast, exhibit greater anxiety with VF, but not VD, when compared with CTR mice. Colonic VD receptor was elevated in VF-treated mice in both sexes, compared with CTR, which was positively correlated to colonic TPH1, a rate-limiting enzyme for serotonin synthesis. Taken together, our data indicate that the effect of VF on anxiety-related behavior is sex-specific, which may partially be attributed to the activation of colonic VD signaling and subsequent serotonin synthesis. The synergistic or additive effect of VD and FOS on mood disorders remained to be investigated.

Supplementation of Methyl-Donor Nutrients to a High-Fat, High-Sucrose Diet during Pregnancy and Lactation Normalizes Circulating 25-Dihydroxycholecalciferol Levels and Alleviates Inflammation in Offspring.

A Western-style diet that is high in fat and sucrose has been shown to alter DNA methylation and epigenetically modify genes related to health risk in offspring. Here, we investigated the effect of a methyl-donor nutrient (MS) supplemented to a high-fat, high-sucrose (HFS) diet during pregnancy and lactation on vitamin D (VD) status and inflammatory response in offspring. After mating, 10-week-old female Sprague-Dawley (SD) rats (n = 10/group) were randomly assigned to one of the four dietary groups during pregnancy and lactation: (1) control diet (CON), (2) CON with MS (CON-MS), (3) HFS, and (4) HFS with MS (HFS-MS). Weanling offspring (three weeks old) were euthanized and sacrificed (n = 8-10/sex/group). The remaining offspring (n = 10/sex/group) were randomly assigned to either a CON or an HFS diet for 12 weeks and sacrificed at 15 weeks of age. Our results indicated that prenatal MS supplementation, but not postnatal diet, restored low vitamin D status and suppressed elevation of proinflammatory cytokine induced by maternal HFS in the offspring. Furthermore, both prenatal and postnatal diets modulated the abundance of Lactobacillus spp. and Bacteroides spp. in the offspring, a shift that was independent of vitamin D status. Collectively, our data support a role for MS in restoring the perturbation of VD status and normalizing maternal HFS-induced inflammation in the offspring. Further investigation is warranted to elucidate the methylation status of VD metabolism-related pathways in the offspring, as well as the immunomodulatory role of vitamin D during the progression of obesity.