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

  • 2024-10-03
  • Microbiology spectrum 12(10)
    • Madhur Wyatt
    • Ankan Choudhury
    • Gabriella Von Dohlen
    • Jeffery L Heileson
    • Jeffrey S Forsse
    • Sumudu Rajakaruna
    • Manja Zec
    • Malak M Tfaily
    • Leigh Greathouse

Study Design

Type
Randomized Controlled Trial (RCT)
Population
healthy adults
Methods
double-blind, randomized, placebo-controlled trial; 4,000 IU vitamin D3 for 12 weeks
Blinding
Double-blind
Duration
12 weeks
Funding
Unclear
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.

Importance

Preventative measures to reduce the rise in early-onset colorectal cancer are of critical need. Both vitamin D, dietary and serum levels, and the gut microbiome are implicated in the etiology of colorectal cancer. By understanding the intimate relationship between vitamin D, the gut microbiome, and its metabolites, we may be able to identify key mechanisms that can be targeted for intervention, including inflammation and metabolic dysfunction. Furthermore, the similarity of vitamin D to cholesterol, which is metabolized by the gut microbiome, gives precedence to its ability to produce metabolites that can be further studied and leveraged for controlling colorectal cancer incidence and mortality.

Research Insights

  • Vitamin D→Improved Gut Microbiota Composition

    Vitamin D₃ significantly increased compositional similarity (P < 0.0001) in the treatment group

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    4,000 IU/day for 12 weeks
  • Vitamin D→Increased 25-hydroxyvitamin D Level

    a significant increase in serum 25-hydroxy-vitamin D (25(OH)D) in the treatment group compared to placebo (P < 0.0001)

    Effect
    Beneficial
    Effect size
    Large
    Dose
    4,000 IU/day for 12 weeks
  • Vitamin D→Reduced Microbial Stability

    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)

    Effect
    Harmful
    Effect size
    Small
    Dose
    4,000 IU/day for 12 weeks
  • Vitamin D→Shifted Fecal Metabolite Network

    vitamin D₃ supplementation resulted in notable metabolic shifts, in addition to resulting in a drastic rewiring of key gut microbial-metabolic associations

    Effect
    Neutral
    Effect size
    Small
    Dose
    4,000 IU/day for 12 weeks
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