Relationship between Circulating Vitamin D Concentration and the Maternal Gut Microbiota during Early Pregnancy in Japanese Women: Results of a Pilot Study of Antenatal Vitamin D<sub>3</sub> Supplementation

Recent studies have demonstrated a significant role for gut microbiota dysbiosis in the pathogenesis of various diseases, pregnancy outcomes, and fetal growth. Vitamin D modulates innate immunity and promotes immune tolerance, suggesting involvement in shaping the gut microbiota. However, the relationship between vitamin D and the gut microbiota during pregnancy has not been evaluated in detail. In this study, we administered a vitamin D₃ supplement (VD) to pregnant Japanese women, starting during the first trimester of pregnancy, and characterized changes in the circulating concentration of vitamin D and the gut microbiome. Sixty-two pregnant women were randomly allocated to three groups. VD was administered at low (200 IU/d), medium (400 IU/d), or high (1,000 IU/d) doses for 8 wk from 12 to 15 wk of pregnancy, and changes in the serum 25-hydroxyvitamin D (25(OH)D) concentration and the gut microbiome were evaluated. Changes in gut microbial taxa abundance were analyzed by Wilcoxon matched-pairs signed-rank test. Before VD administration, 96.8% of the participants were VD-deficient, and none had a sufficient VD concentration. The serum 25(OH)D concentration increased in a dose-dependent manner in all the dose groups. Additionally, the abundance of Fusicatenibacter in the gut microbiota increased in a VD dosedependent manner, with a significant increase observed in the high-dose group. From these results, in pregnant Japanese women, the administration of high-dose VD increases the prevalence of VD sufficiency and alters the gut microbial composition, suggesting that this has benefits for the maternal and neonatal immune systems.