Protective Effect of Akkermansia muciniphila on the Preeclampsia-Like Mouse Model

Preeclampsia (PE) is known as a metabolism-related complication of pregnancy related to gut dysbiosis including the decreased abundance of Akkermansia muciniphila ( A. muciniphila ). However, the modulatory role of A. muciniphila as a supplement for PE remains ambiguous. This study investigated the effect of A. muciniphila administration on PE-like mice and its underlying mechanisms. A total of twenty-four C57BL/6 mice were randomly assigned into three groups. PE-like symptoms were induced by continuous injection of L-NAME intraperitoneally from gestational day (GD) 11 to GD18 combined with oral administration of pasteurized A. muciniphila during GD14-18 or not. Mice were sacrificed at GD19 to collect for further evaluation. Decreased A. muciniphila was observed in a successfully established PE-like model than normotensive pregnant control (NP), inversely correlated to increased systolic blood pressure blood and 24-h proteinuria. After supplementing with A. muciniphila , mice showed significantly minimized blood pressure and protein expression in urine, increased number of pups and weight of both embryos and placentas. In addition, colonies of bacteria, inflammatory cytokines (TNF-α and IL-6), and metabolic products of lipids including TC, FC, and TG were alleviated by A. muciniphila in the placentas. Among proteins linked with bowel barrier functions, diminished 2-AG and growing ZO-1 and occludin were attributable to A. muciniphila. Also, enhanced Treg/Th17 ratios were found in the intestines of mice treated with A. muciniphila . A. muciniphila facilitated alleviating PE-like symptoms and was beneficial as a novel probiotic therapeutic agent for PE.