Title : Vitamin D and the gut microbiota in young women: A cross-sectional metagenomics study
Abstract:
Background: Vitamin D deficiency is prevalent among young women and has been linked to immune dysregulation, metabolic disorders, and gut microbiota alterations. However, large-scale metagenomic studies examining the relationship between serum vitamin D and gut microbial composition, diversity, and function in healthy young women remain scarce.
Methods: Shotgun metagenomic sequencing was performed on stool samples from 283 young women (age 29-36; mean BMI 23.2±4.2kg/m²) in Croatia. Serum 25(OH)D was measured in 187 participants, stratified by supplementation status (124 supplementers vs. 159 non-supplementers). Alpha diversity, the Firmicutes-to-Bacteroidetes ratio, genus-level taxonomy, and functional pathways were assessed. Associations were tested using Spearman correlations and Mann–Whitney U tests with Benjamini–Hochberg correction. A composite low-diversity phenotype was defined to evaluate vitamin D as a potential dysbiosis biomarker.
Results: Vitamin D deficiency was highly prevalent (37% deficient, 29% insufficient, 34% sufficient). Higher serum 25(OH)D correlated with Chao1 richness (ρ=0.147; p=0.045) and Faith’s PD (ρ=0.164; p=0.025). This association was driven by serum concentrations rather than supplementation behavior: Supplementation alone did not improve alpha diversity (all p>0.05), while the correlation remained significant among non-supplementers (ρ=0.256; p=0.010). No association was found with the F/B ratio. Genus-level correlations did not survive FDR correction. Vitamin D deficiency more than doubled the odds of a low-diversity phenotype (OR=2.21; 95% CI: 1.09-4.49), with a dose–response across tertiles (p=0.018) and a negative predictive value of 83.8%. Among 12 routine blood parameters, only iron and CRP were also linked to diversity, making vitamin D the only universally measured, easily modifiable biomarker.
Conclusions: Low serum vitamin D was consistently associated with reduced gut microbial phylogenetic richness, independent of supplementation status, BMI, and age. Achieving adequate circulating concentrations—rather than supplementation per se—appears to be the relevant factor. With its high negative predictive value and easy modifiability, serum 25(OH)D shows promise as a screening biomarker for gut microbial health. Longitudinal studies are needed to clarify causality.
Keywords: Vitamin D, Gut Microbiota, Metagenomics, Alpha Diversity, Dysbiosis, Biomarker, Young Women, Firmicutes-to-Bacteroidetes Ratio, Supplementation.
