Causal associations between gut microbiota and premature rupture of membranes: a two-sample Mendelian randomization study.

Background: Previous study has indicated a potential link between gut microbiota and maternal pregnancy outcomes. However, the causal relationship between gut microbiota and premature rupture of membranes (PROM) remains a topic of ongoing debate.

Methods: A two-sample Mendelian Randomization (MR) study was used to investigate the relationship between gut microbiota and PROM. Genetic data on gut microbiota was obtained from the MiBioGen consortium's largest genome-wide association study (GWAS) (n=14,306). Genetic data on PROM (3011 cases and 104247 controls) were sourced from publicly available GWAS data from the Finnish National Biobank FinnGen consortium. Various methods including Inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were utilized to assess the causal relationship by calculating the odd ratio (OR) value and confidence interval (CI). Sensitivity analyses for quality control were performed using MR-Egger intercept tests, Cochran's Q tests, and leave-one-out analyses.

Results: The IVW method revealed that (IVW, OR=0.773, 95%CI: 0.61-0.981, = 0.034), (IVW, OR=00.736, 95%CI: 0.555-0.977, = 0.034), (IVW, OR=0.734, 95%CI: 0.568-0.947, = 0.017) and (IVW, OR=0.773, 95%CI: 0.566-1.067, = 0.034) were associated with a reduced risk of PROM, while (IVW, OR=1.444, 95%CI: 1.028-2.026, = 0.034), (IVW, OR=1.304, 95%CI: 1.047-1.623, = 0.018) and (IVW, OR=1.282, 95%CI: 1.02-1.611, = 0.033) increased the risk of PROM. Based on the other four supplementary methods, six gut microbiota may have a potential effect on PROM. Due to the presence of pleiotropy (=0.045), should be ruled out. No evidence of horizontal pleiotropy or heterogeneity was found in other microbiota (0.05).

Conclusions: In this study, we have discovered a causal relationship between the presence of specific probiotics and pathogens in the host and the risk of PROM. The identification of specific gut microbiota associated with PROM through MR studies offers a novel approach to diagnosing and treating this condition, thereby providing a new strategy for clinically preventing PROM.