The causality between gut microbiota and ectopic pregnancy based on genome-wide association: A Mendelian randomization study

Ectopic pregnancy represents a prevalent gynecological emergency with incompletely characterized pathophysiology, creating substantial clinical challenges in timely diagnosis and effective management. The causal interplay between gut microbiota and ectopic pregnancy, particularly through plasma proteomics mediation, remains undefined. We derived Gut microbiota GWAS data (n=412) from the Dutch Microbiome Project meta-analysis and Ectopic pregnancy data from IEU OpenGWAS and FinnGen project. The results revealed nine kinds of gut microbiotas demonstrating causal associations with ectopic pregnancy risk. A total of 67 plasma proteins causally impact the risk of ectopic pregnancy. In addition, three kinds of gut microbiotas were mediated by 25 kinds of plasma proteins on ectopic pregnancy. Microbiota enriched in L.rhamnose.degradation.I affected ectopic pregnancy through 22 kinds of plasma proteins. This study establishes causal relationships between specific gut microbial pathways and ectopic pregnancy risk, mediated through distinct plasma protein signatures, providing directions for clinical interventions and future research.