Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice

IF 7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Molecular Metabolism Pub Date : 2024-08-08 DOI:10.1016/j.molmet.2024.102004
Jorge Lopez-Tello , Raymond Kiu , Zoe Schofield , Cindy X.W. Zhang , Douwe van Sinderen , Gwénaëlle Le Gall , Lindsay J. Hall , Amanda N. Sferruzzi-Perri
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引用次数: 0

Abstract

Background

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.

Objective

This study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy.

Methods

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.

Results

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.

Conclusions

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.

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母体肠道双歧杆菌改变了无菌小鼠胎儿大脑的新陈代谢。
背景:最近的研究进展极大地扩展了我们对肠道微生物组对宿主生理和新陈代谢影响的认识。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:本研究探讨了孕期双歧杆菌 UCC2003 在母体肠道定植后对胎儿大脑代谢的影响:方法:在无胚芽妊娠小鼠妊娠期间,在其肠道中定植或不定植布氏双歧杆菌 UCC2003。分析了胎儿大脑的代谢谱,重点是关键代谢物的存在以及关键代谢和细胞通路的表达:结果:母体定植双歧杆菌后,胎儿大脑的代谢发生了显著变化。具体来说,胎儿大脑中的柠檬酸盐、3-羟基异丁酸盐和肉碱等十种代谢物减少了。伴随这些变化的是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通路的表达升高有关,如 PI3K-AKT、AMPK、STAT5 和 Wnt-β-catenin 信号转导,包括其受体 Frizzled-7。此外,HIF-2 蛋白趋于稳定,与细胞生长、轴突生长和线粒体功能有关的基因和蛋白质也发生了改变:结论:孕期母体双歧杆菌的存在在调节胎儿大脑代谢和生长方面起着至关重要的作用。这些研究结果表明,双歧杆菌可改变胎儿大脑的发育,可能为通过微生物群靶向干预来增强妊娠健康和胎儿发育提供新的途径。
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来源期刊
Molecular Metabolism
Molecular Metabolism ENDOCRINOLOGY & METABOLISM-
CiteScore
14.50
自引率
2.50%
发文量
219
审稿时长
43 days
期刊介绍: Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction. We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.
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