Causal Links Between Gut Microbiota and Vitamin Deficiencies: Evidence from Mendelian Randomization Analysis

Vitamin deficiencies, particularly in vitamins A, B12, and D, are prevalent across populations and contribute significantly to a range of health issues. While these deficiencies are well documented, the underlying etiology remains complex. Recent studies suggest a close link between the gut microbiota and the synthesis, absorption, and metabolism of these vitamins. However, the specific causal relationships between the gut microbiota composition and vitamin deficiencies remain poorly understood. Identifying key bacterial species and understanding their role in vitamin metabolism could provide critical insights for targeted interventions.

We conducted a two-sample Mendelian randomization (MR) study to assess the causal relationship between the gut microbiota and vitamin deficiencies (A, B12, D). The genome-wide association study data for vitamin deficiencies were sourced from the FinnGen biobank, and the gut microbiota data were from the MiBioGen consortium. MR analyses included inverse variance-weighted (IVW), MR‒Egger, weighted median, and weighted mode approaches. Sensitivity analyses and reverse causality assessments were performed to ensure robustness and validate the findings.

After FDR adjustment, vitamin B12 deficiency was associated with the class Verrucomicrobiae, order Verrucomicrobiales, family Verrucomicrobiaceae, and genus Akkermansia. Vitamin A deficiency was associated with the phylum Firmicutes and the genera Fusicatenibacter and Ruminiclostridium 6. Additional associations for vitamin B12 deficiency included the Enterobacteriaceae and Rhodospirillaceae and the genera Coprococcus 2, Lactococcus, and Ruminococcaceae UCG002. Vitamin D deficiency was associated with the genera Allisonella, Eubacterium, and Tyzzerella 3. Lachnospiraceae and Lactococcus were common risk factors for both B12 and D deficiency. Sensitivity analyses confirmed the robustness of the findings against heterogeneity and horizontal pleiotropy, and reverse MR tests indicated no evidence of reverse causality.

Our findings reveal a possible causal relationship between specific gut microbiota characteristics and vitamin A, B12 and D deficiencies, providing a theoretical basis for addressing these nutritional deficiencies through the modulation of the gut microbiota in the future and laying the groundwork for related interventions.