Maternal gut microbiome during early pregnancy predicts preterm birth

Preterm birth, the leading cause of infant mortality and morbidity, lacks robust biomarkers for early risk prediction. Here, we characterized the maternal gut microbiome in 5,313 Chinese pregnant women from two independent cohorts and identified eleven genera and one species associated with preterm birth during early pregnancy. We demonstrated that microbial risk scores (MRSs), generated from selected microbial genera or species, could effectively segregate pregnant women with shorter gestational duration and at higher preterm birth risk. The MRS showed interaction with host polygenic susceptibility to amplify preterm birth risk. Among bacteria comprising the MRS, Clostridium innocuum exhibited the most promising replicable microbial feature for preterm birth. The C. innocuum exhibited 17β-estradiol-degrading activity, and the estradiol-degrading gene k141_29441_57, validated through functional prediction and heterologous expression in E. coli, was enriched in women with preterm birth. These findings open new avenues for microbiome-targeted predictive and therapeutic strategies to mitigate adverse pregnancy outcomes.