Causal associations between gut microbiota and adverse pregnancy outcomes: A two-sample Mendelian randomization study

Abstract

Growing evidence indicates that gut microbiota could be closely associated with a variety of adverse pregnancy outcomes (APOs), but a causal link between gut microbiome and APOs has yet to be established. Therefore, in this study, we comprehensively investigated the relationship between gut microbiota and APOs to identify specific causal bacteria that may be associated with the development and occurrence of APOs by conducting a two-sample Mendelian randomization (MR) analysis. The microbiome genome-wide association study (GWAS) from the MiBioGen consortium was used as exposure data, and the GWAS for six common APOs was used as outcome data. Single-nucleotide polymorphisms (SNPs) that significantly correlated to exposure, data obtained from published GWAS, were selected as instrumental variables (IVs). We used the inverse variance-weighted (IVW) test as the main MR analysis to estimate the causal relationship. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were used to confirm the presence of horizontal pleiotropy and to exclude outlier SNPs. We performed Cochran's Q test to assess the heterogeneity among SNPs associated with each bacterium. The leave-one-out sensitivity analysis was used to evaluate whether the overall estimates were affected by a single SNP. Our analysis shows a causal association between specific gut microbiota and APOs. Our findings offer novel insights into the gut microbiota-mediated development mechanism of APOs.

Keywords: Mendelian randomization; adverse pregnancy outcomes; causal relationship; gut microbiota; instrumental variable.