Gut microbiota in dysmenorrhea: causal evidence from Mendelian randomization and microbial-targeted intervention validation.

Background: Dysmenorrhea is a prevalent gynecological disorder with multifactorial pathophysiology, including prostaglandin overproduction, inflammation, and pain sensitization. Emerging evidence suggests that gut microbiota may contribute to pain modulation, although causal relationships remain unclear. Methods: Bidirectional two-sample Mendelian randomization (MR) was performed to investigate causal associations between dysmenorrhea and gut microbiota. Complementary Results: Forward MR analyses revealed that genetic liability to dysmenorrhea influenced the abundance of specific gut taxa, notably reducing Lachnospiraceae genera and increasing Erysipelotrichaceae, which was consistent with observed alterations in PDM rats. Reverse MR provided no robust evidence that gut microbiota causally affect dysmenorrhea. In the PDM model, both ibuprofen and WJZTD produced analgesic effects, but induced distinct microbial signatures: ibuprofen increased the presence of Conclusion: This study demonstrates that dysmenorrhea causally alters gut microbiota composition. The restoration of