Volkova Angelina, Ruggles Kelly, Schulfer Anjelique, Gao Zhan, Ginsberg Stephen D, Blaser Martin J
Institute for Systems Genetics, New York University Grossman School of Medicine, New York, NY 10016, USA.
Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.
iScience. 2021 Jul 15;24(7):102797. doi: 10.1016/j.isci.2021.102797. eCollection 2021 Jul 23.
We have established experimental systems to assess the effects of early-life exposures to antibiotics on the intestinal microbiota and gene expression in the brain. This model system is highly relevant to human exposure and may be developed into a preclinical model of neurodevelopmental disorders in which the gut-brain axis is perturbed, leading to organizational effects that permanently alter the structure and function of the brain. Exposing newborn mice to low-dose penicillin led to substantial changes in intestinal microbiota population structure and composition. Transcriptomic alterations implicate pathways perturbed in neurodevelopmental and neuropsychiatric disorders. There also were substantial effects on frontal cortex and amygdala gene expression by bioinformatic interrogation, affecting multiple pathways underlying neurodevelopment. Informatic analyses established linkages between specific intestinal microbial populations and the early-life expression of particular affected genes. These studies provide translational models to explore intestinal microbiome roles in the normal and abnormal maturation of the vulnerable central nervous system.
我们已经建立了实验系统，以评估生命早期接触抗生素对肠道微生物群和大脑基因表达的影响。该模型系统与人类接触情况高度相关，可能会发展成为一种神经发育障碍的临床前模型，其中肠-脑轴受到干扰，导致组织效应，永久性改变大脑的结构和功能。将新生小鼠暴露于低剂量青霉素会导致肠道微生物群种群结构和组成发生重大变化。转录组改变涉及神经发育和神经精神疾病中受到干扰的途径。通过生物信息学分析，对额叶皮质和杏仁核基因表达也有重大影响，影响了神经发育的多个途径。信息分析建立了特定肠道微生物种群与特定受影响基因的早期表达之间的联系。这些研究提供了转化模型，以探索肠道微生物群在脆弱的中枢神经系统正常和异常成熟中的作用。
