Cell重磅：肠道菌群有助于成功怀孕，防止流产

Core Viewpoint - The research highlights the significant role of gut microbiota in promoting maternal-fetal immune tolerance, which is crucial for preventing miscarriage. It establishes a connection between gut health and pregnancy outcomes, providing new insights for miscarriage prevention [2][17]. Group 1: Changes During Pregnancy - Gut permeability in pregnant mice increases with gestational age, allowing substances to enter the bloodstream more easily. The composition of gut microbiota also changes dynamically, with certain bacteria like Bacteroidetes and Clostridia increasing in number [5]. - The absence or disruption of gut microbiota in germ-free or antibiotic-treated mice leads to a significantly higher rate of miscarriage, indicating that gut microbiota is essential for successful pregnancy [5]. Group 2: Immune Imbalance and Miscarriage - Analysis of immune cells reveals severe immune imbalance at the maternal-fetal interface in mice lacking gut microbiota. Specifically, excessive IFN-γ is identified as a key factor leading to miscarriage [7]. - The study identifies two critical pathways through which gut microbiota influences immune responses: the role of myeloid-derived suppressor cells (MDSCs) in inhibiting IFN-γ production and the presence of RORγt+ regulatory T cells that help maintain immune balance [10]. Group 3: Metabolites and Immune Regulation - Tryptophan metabolites, particularly indole compounds, are found to be abundant in the plasma and amniotic fluid of normally pregnant mice. These metabolites activate the aryl hydrocarbon receptor (AhR), promoting the differentiation of RORγt+ Tregs and the functional maturation of MDSCs [12]. - Supplementation with indole-3-carbinol (I3C), an AhR agonist, restores normal miscarriage rates in germ-free mice, demonstrating the potential for dietary interventions to influence pregnancy outcomes [12]. Group 4: Human Relevance - The research extends beyond mouse models, analyzing human datasets that show reduced MDSC numbers and function, decreased RORγt+ Treg proportions, and lower levels of tryptophan metabolites in the endometrium of patients with recurrent miscarriage [14][15]. - These findings suggest that the gut-placenta immune signaling axis is also significant in human pregnancies, reinforcing the importance of gut health for pregnancy outcomes [17].