中国科学院上海免疫与感染研究所Parag Kundu研究小组近日取得一项新成果。他们的最新研究发现，母体肠道微生物群影响后代干细胞功能。该项研究成果发表在2024年12月11日出版的《细胞—干细胞》上。

据介绍，母体微生物组影响儿童健康。然而，它对后代干细胞的影响，调控发育，仍然知之甚少。

为了研究母体微生物群在调节后代干细胞中的作用，该研究团队使用阿克曼菌（Akkermansia muciniphila）操纵了母体的微生物群。不同的母体微生物组对后代神经元和肠道干细胞的增殖和分化有不同的影响，影响它们的发育轨迹、生理和长期健康。研究人员将改变的母体微生物群移植到无菌小鼠体内，将这些干细胞表型传递给受体的后代。

选择定植阿克曼菌的无菌小鼠的后代没有表现出这些干细胞特征，强调了微生物组多样性的重要性。代谢更活跃的母体微生物组丰富了循环短链脂肪酸（SCFAs）和氨基酸的水平，在后代干细胞的mTOR通路上留下了明显的转录组印记。在怀孕期间阻断mTOR信号可以消除母体微生物组介导的对干细胞的影响。

这些结果表明，母体微生物组在后代干细胞的编程中起着基本作用，并代表了一个有希望的干预目标。

附：英文原文

Title: Maternal gut microbiota influence stem cell function in offspring

Author: Haiyue Dang, Panpan Feng, Shuning Zhang, Lihua Peng, Shuli Xing, Yuchen Li, Xiang Wen, Liqiang Zhou, Shyamal Goswami, Mingbing Xiao, Nick Barker, Philippe Sansonetti, Parag Kundu

Issue&Volume: 2024-12-11

Abstract: The maternal microbiome influences child health. However, its impact on a given offspring’s stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring’s stem cells, we manipulated maternal microbiota using Akkermansia muciniphila. Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients’ offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings’ stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings’ stem cells and represent a promising target for interventions.

DOI: 10.1016/j.stem.2024.10.003

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00365-5