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.