The Role of Vitamin B6 and Folate-Related Pathways Involved in Gut Microbial Composition in the Development of...

Preeclampsia is a pregnancy-related hypertensive disorder affecting about 3%-5% of pregnancies worldwide. Recent traditional observational studies have suggested that the gut microbiota was related to preeclampsia. Some Mendelian randomization (MR) studies have examined the link between gut microbiota and preeclampsia using genetic variants as proxies. However, they were limited to a small number of microbial taxa and did not include microbial metabolic pathways.

The latest large-scale genome-wide association studies (GWAS) data were utilized, which included 7738 participants and profiled both gut microbiota abundance and gut bacterial pathway abundance, totaling 412 indicators. For the outcome, summary statistics for preeclampsia were obtained from a large-scale FinnGen GWAS data set comprising over 110,000 individuals. Multiple MR methods were employed to assess the effects. Sensitivity analyses and the evaluation of heterogeneity and potential pleiotropy were performed.

In total, 29 gut microbiota-related indicators were found to be significantly associated with preeclampsia risk, including 16 microbial metabolic pathways and 13 microbial taxa. Notably, the N¹⁰-formyltetrahydrofolate biosynthesis pathway survived multiple testing correction, while Vitamin B6 pathways were nominally significant. Vitamin B6 and folate pathways which are involved in Streptococcus thermophilus, might regulate immune responses, oxidative stress, and energy metabolism, thus modifying preeclampsia risk.

This study suggested Vitamin B6 and folate pathways potentially related to Streptococcus thermophilus, are significantly associated with preeclampsia risk. These findings suggested that gut microbiota might represent a novel, modifiable risk factor for preeclampsia, offering potential avenues for early prediction and prevention through microbiota-targeted strategies such as dietary interventions or probiotic supplementation.