Limosilactobacillus reuteri ameliorates preeclampsia in mice via improving gut dysbiosis and endothelial dysfunction

Abstract

Background: As a leading cause of maternal and neonatal morbidity and mortality, preeclampsia (PE) remains enigmatic. We confirmed that PE is associated with gut dysbiosis. However, whether probiotics could improve PE via regulating gut microbiota remains unclear. Exploring specific probiotic that could alleviate PE by modulating gut microbiota and elucidating detailed mechanisms will be essential for treating PE.

Methods: PE model was induced by nitric oxide (NO) inhibition with L-NAME in mice, and treated with Limosilactobacillus reuteri (L. reuteri). 16 S rDNA analysis was conducted on feces from mice. In vitro and in vivo experiments were performed to explore the roles and mechanisms of L. reuteri in PE.

Results: NO inhibition by L-NAME induced PE and gut dysbiosis in mice, characterized by differential gut microbiome, reduced alpha diversity, and markedly decreased abundance of Lactobacillales and L. reuteri. Importantly, L. reuteri could improve PE induced by L-NAME in mice, and ameliorate the gut dysbiosis of PE mice, including restorative gut microbiota composition, increased alpha diversity, and upregulated L. reuteri content. Moreover, L. reuteri could improve NO synthesis, angiogenesis, inflammation and oxidative stress of PE mice. Consistently, L. reuteri could ameliorate NO synthesis, endothelial dysfunction and inflammation mediated by L-NAME in vitro.

Conclusions: Our results reveal that L. reuteri could ameliorate PE induced by NO inhibition in mice via improving gut dysbiosis and endothelial dysfunction, supporting gut microbiota serving as therapeutic target for treating PE originated from endothelial dysfunction and L. reuteri protecting patients from PE via modulating gut microbiota and endothelial function.

Keywords: Endothelial dysfunction; Gut dysbiosis; Limosilactobacillus reuteri; Nitric oxide; Preeclampsia.