Department of Physiology, Development, and Neuroscience, Centre for Trophoblast Research, University of Cambridge, Cambridge, UK; Department of Physiology, Faculty of Medicine. Autonomous University of Madrid, Spain.
Food, Microbiome & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK; Institute of Microbiology & Infection, University of Birmingham, Birmingham, UK; Department of Microbes, Infection & Microbiomes, School of Infection, Inflammation & Immunology, University of Birmingham, Birmingham, UK.
Mol Metab. 2024 Oct;88:102004. doi: 10.1016/j.molmet.2024.102004. Epub 2024 Aug 8.
Recent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored.
This study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy.
Germ-free pregnant mice were colonized with or without B. breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways.
Maternal colonization with B. breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-β-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function.
The presence of maternal B. breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions.
最近的进展极大地拓展了我们对肠道微生物组对宿主生理和代谢影响的理解。然而，某些微生物在妊娠健康和胎儿发育中的具体作用仍未得到充分探索。
本研究旨在探讨母体肠道定植双歧杆菌短双歧杆菌 UCC2003 对妊娠期间胎儿大脑代谢的影响。
无菌妊娠小鼠在妊娠期间用或不用双歧杆菌短双歧杆菌 UCC2003 定植。分析胎儿大脑的代谢谱，重点关注关键代谢物的存在和关键代谢和细胞途径的表达。
母体定植双歧杆菌导致胎儿大脑发生显著代谢变化。具体来说，包括柠檬酸、3-羟基异丁酸和肉碱在内的十种代谢物在胎儿大脑中减少。这些变化伴随着参与葡萄糖和支链氨基酸摄取的转运体的丰度增加。此外，补充这种细菌与关键代谢途径的表达增加有关，如 PI3K-AKT、AMPK、STAT5 和 Wnt-β-catenin 信号通路，包括其受体 Frizzled-7。此外，HIF-2 蛋白稳定，与细胞生长、轴突发生和线粒体功能相关的基因和蛋白质发生修饰。
妊娠期间母体双歧杆菌的存在在调节胎儿大脑代谢和生长中起着至关重要的作用。这些发现表明双歧杆菌可以修饰胎儿大脑发育，为通过微生物组靶向干预增强妊娠健康和胎儿发育提供新的途径。
