Department of Pediatrics, The University of Chicago, Pritzker School of Medicine, Chicago, IL, USA.
Magnetic Resonance Imaging and Spectroscopy Laboratory, The University of Chicago, Department of Radiology, Chicago, IL, USA.
Gut Microbes. 2023 Jan-Dec;15(1):2178800. doi: 10.1080/19490976.2023.2178800.
Maternal immune activation (MIA) derived from late gestational infection such as seen in chorioamnionitis poses a significantly increased risk for neurodevelopmental deficits in the offspring. Manipulating early microbiota through maternal probiotic supplementation has been shown to be an effective means to improve outcomes; however, the mechanisms remain unclear. In this study, we demonstrated that MIA modeled by exposing pregnant dams to lipopolysaccharide (LPS) induced an underdevelopment of the blood vessels, an increase in permeability and astrogliosis of the blood-brain barrier (BBB) at prewean age. The BBB developmental and functional deficits early in life impaired spatial learning later in life. Maternal () supplementation starting at birth rescued the BBB underdevelopment and dysfunction-associated cognitive function. Maternal -mediated alterations in β-diversity of the microbial community and metabolic responses in the offspring provide mechanisms and potential targets for promoting BBB integrity and long-term neurodevelopmental outcomes.
母体免疫激活(MIA)源于晚期妊娠感染,如绒毛膜羊膜炎,会显著增加后代神经发育缺陷的风险。通过母体益生菌补充来操纵早期微生物群已被证明是改善结局的有效手段;然而,其机制仍不清楚。在这项研究中,我们表明,通过用脂多糖(LPS)暴露怀孕的母鼠来模拟 MIA,会导致血管发育不良、血脑屏障(BBB)的通透性增加和星形胶质细胞增生,在断奶前就出现这种情况。生命早期 BBB 发育和功能缺陷会损害以后的空间学习能力。从出生开始补充 (),可以挽救 BBB 发育不良和功能障碍相关的认知功能。母体介导的微生物群落β多样性改变和后代的代谢反应为促进 BBB 完整性和长期神经发育结果提供了机制和潜在靶点。