Abstract：
Stress during pregnancy is often linked with increased incidents of neurodevelopmental disorders, including cognitive impairment. Here, we report that stress during pregnancy leads to alterations in the intestinal flora, which negatively affects the cognitive function of offspring. Cognitive impairment in stressed offspring can be reproduced by transplantation of cecal contents of stressed pregnant rats (ST) to normal pregnant rats. In addition, gut microbial dysbiosis results in an increase of β-guanidinopropionic acid in the blood, which leads to an activation of the adenosine monophosphate-activated protein kinase (AMPK) and signal transducer and activator of transcription 3 (STAT3) in the fetal brain. Moreover, β-guanidinopropionic acid supplementation in pregnant rats can reproduce pregnancy stress-induced enhanced glial differentiation of the fetal brain, resulting in impaired neural development. Using probiotics to reconstruct maternal microbiota can correct the cognitive impairment in the offspring of pregnant stressed rats. These findings suggest that microbial reconstitution reverses gestational stress-induced cognitive impairment and synaptic deficits in male rat offspring.
摘要：
怀孕期间的压力通常与神经发育障碍事件的增加有关，包括认知障碍。这里,我们报告说，怀孕期间的压力会导致肠道菌群的改变，这会对后代的认知功能产生负面影响。通过将应激妊娠大鼠（ST）的盲肠内容物移植到正常妊娠大鼠，可以复制应激后代的认知障碍。此外,肠道微生物菌群失调导致血液中β-胍丙酸的增加，导致胎儿大脑中单磷酸腺苷激活的蛋白激酶（AMPK）和信号转导和转录激活因子3（STAT3）的激活。此外，孕鼠补充β-胍基丙酸可再现妊娠应激诱导的胎脑胶质细胞分化增强,导致神经发育受损。使用益生菌重建母体微生物区系可以纠正妊娠应激大鼠后代的认知障碍。这些发现表明，微生物重建可以逆转妊娠应激引起的雄性大鼠后代的认知障碍和突触缺陷。
