Exploring the genetically predicted gut microbiota-reproductive axis: Impact on anti-Müllerian hormone levels

This study investigates the causal relationship between gut microbial composition and circulating anti-Müllerian hormone (AMH) levels using Mendelian randomization (MR) to determine whether specific gut microbial profiles causally influence AMH levels.

The two-sample MR approach was employed using genome-wide association study (GWAS) summary statistics for gut microbiota and AMH levels. Instrumental variables were selected based on single-nucleotide polymorphisms that met the MR validity assumptions. Data on gut microbiota were sourced from the MiBioGen consortium involving 14 306 individuals, whereas AMH level data were obtained from a GWAS meta-analysis of 7049 premenopausal women. Multiple MR methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode, were used to assess causal associations.

Mendelian randomization analysis identified four bacterial groups that were significantly associated with AMH levels (P < 0.05) using the IVW method. The class Bacilli, order Lactobacillales, and genus Roseburia were positively associated with AMH levels, whereas the genus Flavonifractor was negatively associated with AMH levels. After adjusting for the false discovery rate, none of these associations remained statistically significant. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy, and leave-one-out analyses confirmed the robustness of the results, with consistent direction across methods (except for the genus Flavonifractor).

Our findings provide preliminary genetic evidence that higher abundance of the class Bacilli, order Lactobacillales, and genus Roseburia may increase AMH levels, whereas the genus Flavonifractor might decrease AMH levels. Further research with larger sample sizes is needed to confirm these suggestive associations and explore the underlying mechanisms for potential therapeutic implications in reproductive health.