Probiotic Lactobacillus rhamnosus prevents preeclampsia progression by restoring gut– placenta microbial homeostasis and regulating placental LysoPC metabolism

Background Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that poses a serious threat to maternal and fetal health. PE progression is closely associated with gut microbiota dysbiosis and inflammation; however, effective microbiota-targeted interventions remain limited. Methods In this study, a PE rat model was established by administering a low dose of lipopolysaccharide (LPS) in early pregnancy to explore the potential protective effects and underlying mechanisms of Lactobacillus rhamnosus (LR) supplementation during gestation. We measured blood pressure, urinary protein levels, and placental indices, performed 16S rRNA sequencing to profile changes in gut and placental microbiota, and conducted untargeted metabolomics to identify placental differential metabolites and analyze their correlations with microbial taxa. Results The results showed that LPS induced significant hypertension and proteinuria in pregnant rats, reduced α diversity of gut microbiota, and markedly decreased the abundance of butyrate-producing bacteria such as Roseburia and Clostridia_UCG-014 . Concurrently, pro-inflammatory lysophosphatidylcholines (LysoPCs; LysoPC 16:1, 16:2, and 10:0) were significantly elevated in the placenta. LR intervention effectively lowered systolic, diastolic, and mean arterial pressures, attenuated proteinuria, and restored gut microbial balance by increasing the abundance of beneficial taxa and enhancing microbial diversity. Notably, LR supplementation also significantly reduced placental LysoPC accumulation, suggesting its potential as a metabolic intervention target. Furthermore, we identified four key genera ( Roseburia , Clostridia_UCG-014 , Eubacterium_siraeum_group , and Lachnospiraceae_UCG-006 ) that exhibited similar trends in both placental and cecal samples, supporting the concept of gut–placenta axis microbial translocation. Correlation analyses revealed close associations between these core microbial genera and differential placental metabolites, indicating that LR may alleviate PE phenotypes by modulating microbe–metabolite networks. Conclusions Our study provides new experimental evidence and theoretical support for probiotic intervention during pregnancy to alleviate preeclampsia, and also identifies potential microbial and metabolic targets for future exploration of PE prevention and treatment strategies.