Randomized control trial of moderate dose vitamin D alters microbiota stability and metabolite networks in healthy adults

Evidence indicates that both vitamin D and the gut microbiome are involved in the process of colon carcinogenesis. However, it is unclear what effects supplemental vitamin D₃ has on the gut microbiome and its metabolites in healthy adults. We conducted a double-blind, randomized, placebo-controlled trial to identify the acute and long-term microbiota structural and metabolite changes that occur in response to a moderate dose (4,000 IU) of vitamin D₃ for 12 weeks in healthy adults. Our results demonstrated a significant increase in serum 25-hydroxy-vitamin D (25(OH)D) in the treatment group compared to placebo (P < 0.0001). Vitamin D₃ significantly increased compositional similarity (P < 0.0001) in the treatment group, and enriched members of the Bifidobacteriaceae family. We also identified a significant inverse relationship between the percent change in serum 25(OH)D and microbial stability in the treatment group (R = -0.52, P < 0.019). Furthermore, vitamin D₃ supplementation resulted in notable metabolic shifts, in addition to resulting in a drastic rewiring of key gut microbial-metabolic associations. In conclusion, we show that a moderate dose of vitamin D₃ among healthy adults has unique acute and persistent effects on the fecal microbiota, and suggest novel mechanisms by which vitamin D may affect the host-microbiota relationship.