美国加州大学洛杉矶分校Helen E. Vuong课题组取得一项新成果。他们的最新研究表明小鼠母体微生物组可以调节胎儿的神经发育。2020年9月23日，《自然》在线发表了这一成果。
研究人员探究了小鼠母体肠道微生物组的缺失和选择性重建如何影响胎儿的神经发育。抗生素处理和饮食无菌水母体产生的胚胎中，其大脑表现出与轴突发生相关基因的表达减少、丘脑皮层轴突不足以及响应细胞外源因子的丘脑轴突生长受损。微生物群落耗竭后定植既定菌落的母体可防止胎儿脑基因表达和丘脑皮质轴突发生异常。
代谢组学分析表明，母体微生物组调节母体血清和后代胎儿脑中的许多小分子。选择微生物群依赖性代谢产物可促进胎儿丘脑外植体的轴突生长。此外，孕妇补充这些代谢物可消除胎儿丘脑皮层轴突缺陷。对孕期母体微生物组和微生物代谢产物处理产生的成年后代在两种厌恶型体感行为模型中表现出触觉敏感性改变，但在许多其他感觉运动行为上没有明显差异。
总之，该发现表明，母体肠道微生物组可能通过微生物产生的代谢产物向发育中的胎儿大脑神经元发出信号，从而促进胎儿丘脑皮层轴突的发育。
据悉，由于应对怀孕期间感染、饮食改变和压力等挑战而导致的孕妇肠道微生物组“代谢失调”，越来越多地与后代脑功能和行为异常相联系起来。但是，尚不清楚母体肠道微生物组是否在关键的产前时期和没有环境挑战的情况下影响胎儿的神经发育。
附：英文原文
Title: The maternal microbiome modulates fetal neurodevelopment in mice
Author: Helen E. Vuong, Geoffrey N. Pronovost, Drake W. Williams, Elena J. L. Coley, Emily L. Siegler, Austin Qiu, Maria Kazantsev, Chantel J. Wilson, Tomiko Rendon, Elaine Y. Hsiao
Issue&Volume: 2020-09-23
Abstract: ‘Dysbiosis’ of the maternal gut microbiome, in response to challenges such as infection1, altered diet2 and stress3 during pregnancy, has been increasingly associated with abnormalities in brain function and behaviour of the offspring4. However, it is unclear whether the maternal gut microbiome influences neurodevelopment during critical prenatal periods and in the absence of environmental challenges. Here we investigate how depletion and selective reconstitution of the maternal gut microbiome influences fetal neurodevelopment in mice. Embryos from antibiotic-treated and germ-free dams exhibited reduced brain expression of genes related to axonogenesis, deficient thalamocortical axons and impaired outgrowth of thalamic axons in response to cell-extrinsic factors. Gnotobiotic colonization of microbiome-depleted dams with a limited consortium of bacteria prevented abnormalities in fetal brain gene expression and thalamocortical axonogenesis. Metabolomic profiling revealed that the maternal microbiome regulates numerous small molecules in the maternal serum and the brains of fetal offspring. Select microbiota-dependent metabolites promoted axon outgrowth from fetal thalamic explants. Moreover, maternal supplementation with these metabolites abrogated deficiencies in fetal thalamocortical axons. Manipulation of the maternal microbiome and microbial metabolites during pregnancy yielded adult offspring with altered tactile sensitivity in two aversive somatosensory behavioural tasks, but no overt differences in many other sensorimotor behaviours. Together, our findings show that the maternal gut microbiome promotes fetal thalamocortical axonogenesis, probably through signalling by microbially modulated metabolites to neurons in the developing brain.
DOI: 10.1038/s41586-020-2745-3
Source: https://www.nature.com/articles/s41586-020-2745-3
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
