(P11-007-23) Characterize the Combination Effects of Prebiotic Fiber and Vitamin D on Systemic and Colonic Vitamin D Signaling in Mice

Objectives: Insufficiency levels of vitamin D have shown to exacerbate several complications that is consistent with gut dysbiosis, such as compromised immune function, decreased cognitive functions, and perturbed metabolic health. To date, the interactions between gut microbiota and vitamin D metabolism remains unclear. This study aims to investigate if modulation of gut microbiota compositions can affect systemic and colonic vitamin D signaling.

Methods: Male and female C57BL/6J mice at 6-week-old were randomized into 6 groups to receive the following dietary regimens (n = 10/sex/group) for 8 weeks: 1) standard AIN-93G control diet (CTR), 2) CTR + antibiotics (AB), 3) CTR + 5000 IU vitamin D₃ (VD), 4) VD + antibiotics (VD + AB), 5) VD + frutooligosaccharides (VF), and 6) VF + antibiotics (VF + AB). Kidney and colon mucosa was collected at the end of the study for analysis of mRNA expressions.

Results: Vitamin D status, as indicated by circulating levels of 25-hydroxycholecalciferol (25D), was higher in all VD-supplemented groups regardless of antibiotics treatment, compared to CTR and AB, respectively. Sex difference was observed (P < 0.001), in which female mice exhibited higher level of circulating 25D compared to males. Systemic VD signaling, indicated by renal vitamin D receptor (VDR) mRNA expressions, was 70% lower in VD mice when compared to CTR mice (P = 0.012), but no difference was observed in VF mice when compared to VD or CTR mice, respectively. Antibiotics did not affect systemic VD signaling. In contrast, mRNA expressions of colonic VDR in VF mice was 5-fold higher than in CTR mice (P < 0.001), and that antibiotics downregulated colonic VDR mRNA expressions in VF mice by 52% (P = 0.032). No difference in colonic VDR mRNA expressions was detected between CTR and VD mice nor it was affected by antibiotics. No sex differences were observed in both renal and colon VDR mRNA expressions.

Conclusions: Our results suggested that the modulation of gut microbiota by prebiotic fiber alters colonic VD signaling but not systemic VD signaling. Because VD can regulate immune response, activation of colonic VD signaling via prebiotic fibers could serve as a potential strategy for prevention of gastrointestinal inflammation.

Funding Sources: This study was supported by Texas State University Startup Funds granted to Dr. Gar Yee Koh.