Gar Yee Koh, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: The immunomodulatory of vitamin D (VD) is widely recognized in the recent decade as suboptimal level of VD is often associated with increased risk of metabolic complications and immune dysfunctions. Activation of vitamin D receptor (VDR) in the ileum has been shown to regulate Paneth cell specific alpha-defensins, a large family of antimicrobial peptides, and hence may serve as a potential mechanism to maintain intestinal homeostasis. However, the combination effect of VD and FOS on alpha-defensins secretion by the small intestine is lacking. Here, we aim to examine the effect of VD, alone or in combination with FOS, on VDR signaling and expressions of alpha defensins in the small intestine.
Methods: Male and female C57BL/6J mice at 6-week-old were randomized into 3 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 + frutooligosaccharides (VF). Small intestinal mucosa was collected for analysis of mRNA expressions of VDR, alpha-defensin 5 (DFa5), and alpha-defensin 1 (DFa1).
Results: VD activation in the small intestine, as indicated by mRNA expression of VDR, was 54% lower in VF-treated mice compared to VD mice (P = 0.01) and 42% lower when compared to CTR mice (P = 0.07), and that the effects were mainly observed in female mice. Similarly, the mRNA expressions of DFa5 and DFa1 were downregulated by VF treatment compared to CTR and VD, respectively. Further, we demonstrated a positive correlation between the mRNA expression of VDR and mRNA expressions of DFa5 (Pearson’s = 0.51; P < 0.001) and DFa1 (Pearson’s = 0.52; P = 0.002), respectively.
Conclusions: Our data demonstrated that the combination of FOS and VD, but not VD alone, suppressed VDR activation and its downstream target of the antimicrobial peptides, DFa5 and DFa1. As FOS has been shown to modulate gut microbiota, our results may suggest a potential interaction between the gut microbiota and VDR, a mechanism that could impact the subsequent productions of alpha defensins. Future investigations are warranted to determine the health implications of VDR activation and subsequent alpha defensins production, as well as the profile of gut microbiome in these mice.
Funding Sources: This study was supported by Texas State University Startup Funds granted to Dr. Gar Yee Koh.
