Pasteurized Akkermansia muciniphila ameliorates insulin resistance by reducing placental inflammation in GDM mouse model

Abstract

Gestational diabetes mellitus (GDM) is a common and serious complication during pregnancy. Depleted next-generation probiotic, Akkermansia muciniphila (AKK) in GDM women indicates its potential on GDM prevention. However, the functions and mechanisms of AKK on GDM remain unclear. Due to the limited strategies for GDM therapy, combined with the anaerobic properties of AKK, herein, we reported pasteurized AKK functions as novel postbiotics which ameliorated glucose intolerance and insulin resistance in the GDM mouse model induced by high-fat diet (HFD) feeding combined with STZ. The oral administration of pasteurized AKK enhanced glucose homeostasis and alleviated placental inflammation in the GDM mouse model. Specifically, placental macrophage polarization was transferred by AKK treatment. In addition, the outer membrane protein of AKK, Amuc_1100, mimicked anti-inflammatory properties and improvement of GDM, which served as an effector protein. These findings demonstrate that oral AKK supplementation alleviated placental inflammatory responses through modulating macrophage polarization. Mechanically, we uncovered that a heat-stable outer membrane protein of AKK, Amuc_1100, mimics the anti-diabetic properties of pasteurized AKK through oral administration. Taken together, our findings demonstrated an effective treatment of GDM from the perspective of potential probiotic agents.