Observational and Causal Association of Blood Vitamin D with Gut Microbiota: Evidence from a Prospective Cohort and Mendelian Randomization Analysis
Abstract Objectives Little is known about the relationship between blood vitamin D status and gut microbiota. We aimed to investigate the prospective association of blood 25-hydroxyvitamin D (25(OH)D) with gut microbiota and assess their potential causal relationship. Methods Our study was based on the Guangzhou Nutrition and Health Study, a community-based prospective cohort in China. We examined the prospective association of baseline 25(OH)D with gut microbiota diversity, composition and individual taxa (mean 4.3 years of follow-up) (n = 1757) using linear or logistic regression models. Using genetic variants as instrument variables, we used a Mendelian randomization analysis to assess the causal relationship between 25(OH)D and gut microbiota. Results Higher blood 25(OH)D levels were associated with higher alpha-diversity indicators: including Chao1 index, Shannon index and Observed OUTs index (all P < 0.01, comparing extreme quartiles (Q) of 25(OH)D). Significant difference (P < 0.01) in beta-diversity was also found between Q1 and Q4 of 25(OH)D. Meanwhile, high 25(OH)D (Q4 versus Q1) was prospectively associated with the gut enterotype (Prevotella) and with differences in 37 individual taxa of gut microbiota (P < 0.05). Mendelian randomization analysis suggested that higher 25(OH)D was causally associated with higher abundance of Erysipelotrichaceae and with presence of Rothia. Conclusions Blood vitamin D status is prospectively associated with future gut microbiota diversity and composition. Available evidence suggests a potential causal association of vitamin D with some gut bacteria, and more research is needed to confirm these results. Funding Sources National Natural Science Foundation of China (81,903,316, 81,773,416).