Association Between Circulating Vitamin K Levels, Gut Microbiome, and Type 1 Diabetes: A Mendelian Randomization Study

Background/objectives: Nutritional deficiencies have been proposed as possible etiological causes for autoimmune diseases, among which type 1 diabetes (T1D). Vitamin K (VK) has potentially positive effects on type 2 diabetes, but its role on T1D in humans remains largely unknown. We aimed to examine the presence of a causal association between VK and T1D using a Mendelian randomization (MR) approach.

Methods: Genetic variants from a genome-wide association study (GWAS) for VK (N = 2138 Europeans) were used as instruments in our two-sample MR study to investigate whether circulating VK levels are causally associated with the risk of T1D in a large European T1D GWAS cohort (18,942 cases/520,580 controls). Through a multivariable MR (MVMR), the effects of both VK and specific gut microbiota on T1D were investigated given that the gut microbiome synthesizes VK.

Results: We found that changes in levels of circulating VK did not affect T1D risk in our univariate two-sample MR, but this study had limited power to detect small effects of VK (OR for T1D of less than 0.8). However, our MVMR indicated a suggestive association of VK with the risk of T1D adjusting for two different gut microbiome populations.

Conclusions: In conclusion, VK levels are unlikely to significantly affect the risk of T1D, but small effects cannot be excluded, and the role of gut microbiome in this association should be further investigated.