Bidirectional Two-Sample, Two-Step Mendelian Randomisation Study Reveals Mediating Role of Gut Microbiota Between Vitamin B Supplementation and Alzheimer's Disease.

Objectives: Alzheimer's disease (AD) is a devastating neurodegenerative disorder with a complex aetiology. The aims of this study were to investigate the relationship between vitamin B supplementation and AD risk and to explore the potential mediating effect of the gut microbiota in this relationship.

Methods: We employed a Mendelian randomisation analysis to examine the association between different vitamin B supplementation modalities (vitamin B, folic acid, B, and vitamin B complex tablets) and AD risk. Univariate Mendelian randomisation with inverse-variance weighting was used. Additionally, mediation analyses were conducted to identify the potential mediating effects of 119 known bacterial genera.

Results: The univariate Mendelian randomisation analyses showed no significant direct associations between individual vitamin B supplements or vitamin B complex tablets and AD risk. However, several gut bacterial genera were significantly associated with AD risk. (NK4A136 group), Paraprevotella, Slackia, and Bifidobacterium were associated with reduced AD risk, while (UCG011), , group, and were associated with increased AD risk. The mediation analysis revealed that (NK4A136 group), (UCG011), and fully mediated the causal relationships between vitamin B, B, and B complex supplementation, respectively, and AD risk.

Conclusions: This study provides evidence suggesting that certain gut microbiota genera are significantly associated with AD risk and may mediate the relationship between vitamin B supplementation and AD risk. These findings offer new insights into the variable effectiveness of B vitamins in treating neurodegenerative diseases and suggest potential new strategies for AD treatment and prevention.