肠道微生物群在精神分裂症发展中的作用。

The role of the gut microbiome in the development of schizophrenia.

机构信息

Department of Psychiatry, Trinity College Dublin, Ireland.

Department of Psychiatry and Neurobehavioral Science, University College Cork, Ireland.

出版信息

Schizophr Res. 2021 Aug;234:4-23. doi: 10.1016/j.schres.2020.02.010. Epub 2020 Apr 23.

Abstract

Schizophrenia is a heterogeneous neurodevelopmental disorder involving the convergence of a complex and dynamic bidirectional interaction of genetic expression and the accumulation of prenatal and postnatal environmental risk factors. The development of the neural circuitry underlying social, cognitive and emotional domains requires precise regulation from molecular signalling pathways, especially during critical periods or "windows", when the brain is particularly sensitive to the influence of environmental input signalling. Many of the brain regions involved, and the molecular substrates sub-serving these domains are responsive to life-long microbiota-gut-brain (MGB) axis signalling. This intricate microbial signalling system communicates with the brain via the vagus nerve, immune system, enteric nervous system, enteroendocrine signalling and production of microbial metabolites, such as short-chain fatty acids. Preclinical data has demonstrated that MGB axis signalling influences neurotransmission, neurogenesis, myelination, dendrite formation and blood brain barrier development, and modulates cognitive function and behaviour patterns, such as, social interaction, stress management and locomotor activity. Furthermore, preliminary clinical studies suggest altered gut microbiota profiles in schizophrenia. Unravelling MGB axis signalling in the context of an evolving dimensional framework in schizophrenia may provide a more complete understanding of the neurobiological architecture of this complex condition and offers the possibility of translational interventions.

摘要

精神分裂症是一种异质的神经发育障碍,涉及遗传表达的复杂和动态双向相互作用以及产前和产后环境风险因素的积累。涉及社会、认知和情感领域的神经回路的发育需要来自分子信号通路的精确调节,特别是在大脑对环境输入信号特别敏感的“关键期”或“窗口期”期间。许多涉及的大脑区域以及服务于这些领域的分子基质都对终生微生物群-肠-脑 (MGB) 轴信号有反应。这个错综复杂的微生物信号系统通过迷走神经、免疫系统、肠神经系统、肠内分泌信号以及微生物代谢产物(如短链脂肪酸)的产生与大脑进行交流。临床前数据表明,MGB 轴信号会影响神经传递、神经发生、髓鞘形成、树突形成和血脑屏障发育,并调节认知功能和行为模式,例如社交互动、压力管理和运动活动。此外,初步的临床研究表明精神分裂症患者的肠道微生物组谱发生了改变。在精神分裂症不断发展的多维框架中揭示 MGB 轴信号,可能会更全面地了解这种复杂疾病的神经生物学结构,并提供转化干预的可能性。

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