Causal Effects of Gut Microbiota on Female Reproductive Tract Inflammation and Infertility: A Mendelian Randomization Study

Abstract

Background Studies indicate a potential connection between gut microbiota and reproductive health issues in women, such as inflammation and infertility. However, the exact relationship remains uncertain, highlighting the need for further research. Results A two-sample Mendelian Randomization (MR) analysis was conducted to investigate the relationship between gut microbiota and pelvic inflammatory diseases and infertility. The study identified that specific gut microbiota, such as Lachnospiraceae UCG001 and Ruminococcus 2, increased the risk of inflammatory disorders in female pelvic organs (OR [95%CI]: 1.13 [1.01–1.26] and 1.16 [1.03–13.1], respectively). In contrast, Butyricicoccus and Prevotella 7 were associated with a reduced risk. Further validation with another dataset confirmed Butyricicoccus's role in decreasing pelvic inflammatory disease risk. The study also found a causal relationship between gut microbiota and inflammation in specific pelvic organs, including salpingitis and oophoritis, uterine inflammation, cervical inflammation, and vulvar or vaginal inflammation. Regarding female infertility, Faecalibacterium was linked to an increased risk (1.31 [1.08–1.60]), while genera like Erysipelotrichaceae UCG003 and Ruminococcus (torques group) were associated with lower risks. Further analyses showed a causal connection between gut microbiota and various types of infertility, including anovulation, tubal factors, and others. These results were further confirmed by sensitivity analysis, and no reverse causation was found. Conclusions This study provides compelling evidence for the causal relationship between gut microbiota and female reproductive health. Identification of specific bacterial genera associated with increased or decreased risk offers new possibilities for early diagnosis and targeted treatment.