Dietary, metabolic and gut microbiota influences on primary ovarian failure: a two-sample Mendelian randomization study.

Background and objectives: Previous studies have reported there were associations between ovarian function and dietary factors, metabolic factors and gut microbiota. However, it is unclear whether causal associations exist. We aimed to explore the causal relationship of these factors with risk of primary ovarian failure (POF).

Methods and study design: Two-sample Mendelian randomization (MR) analysis was performed to genetically predict the causal effects of dietary and metabolic factors and gut microbiota on POF. The inverse variance weighted (IVW) method was used as the primary statistical method. A series of sensitivity analyses, including weighted median, MR-Egger, simple mode, weighted mode methods, and leave-one-out analysis, were conducted to assess the robustness of the MR analysis results.

Results: IVW analysis revealed that cigarettes smoked per day, coffee intake and cooked vegetable intake were not causally correlated with POF at the genetic level. However, POF were associated with fresh fruit intake, BMI, Eubacterium (hallii group), Eubacterium (ventriosum group), Adlercreutzia, Intestinibacter, Lachnospiraceae (UCG008), and Terrisporobacter. These findings were robust according to extensive sensitivity analyses.

Conclusions: This study identified several dietary factors, metabolic factors and gut microbiota taxa that may be causally implicated in POF, potentially offering new therapeutic targets.