Mechanisms by which microbiome-derived metabolites exert their impacts on neurodegeneration

IF 6.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lara Kern, Ignacio Mastandrea, Anna Melekhova, Eran Elinav
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引用次数: 0

Abstract

Recent developments in microbiome research suggest that the gut microbiome may remotely modulate central and peripheral neuronal processes, ranging from early brain development to age-related changes. Dysbiotic microbiome configurations have been increasingly associated with neurological disorders, such as neurodegeneration, but causal understanding of these associations remains limited. Most mechanisms explaining how the microbiome may induce such remote neuronal effects involve microbially modulated metabolites that influx into the ‘sterile’ host. Some metabolites are able to cross the blood-brain barrier (BBB) to reach the central nervous system, where they can impact a variety of cells and processes. Alternatively, metabolites may directly signal to peripheral nerves to act as neurotransmitters or exert modulatory functions, or impact immune responses, which, in turn, modulate neuronal function and associated disease propensity. Herein, we review the current knowledge highlighting microbiome-modulated metabolite impacts on neuronal disease, while discussing unknowns, controversies and prospects impacting this rapidly evolving research field.
微生物衍生代谢物对神经退行性病变产生影响的机制
微生物组研究的最新进展表明,肠道微生物组可能会远程调节中枢和外周神经元过程,包括从早期大脑发育到与年龄相关的变化。微生物组配置失调与神经系统疾病(如神经变性)的关系日益密切,但对这些关联的因果关系的了解仍然有限。解释微生物群如何诱发神经元远端效应的大多数机制都涉及微生物调节的代谢物流入 "无菌 "宿主体内。一些代谢物能够穿过血脑屏障(BBB)到达中枢神经系统,对各种细胞和过程产生影响。另外,代谢物也可能直接向周围神经发出信号,充当神经递质或发挥调节功能,或影响免疫反应,进而调节神经元功能和相关疾病倾向。在此,我们将回顾目前的知识,重点介绍微生物组调控的代谢物对神经元疾病的影响,同时讨论影响这一快速发展的研究领域的未知因素、争议和前景。
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来源期刊
Cell Chemical Biology
Cell Chemical Biology Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
14.70
自引率
2.30%
发文量
143
期刊介绍: Cell Chemical Biology, a Cell Press journal established in 1994 as Chemistry & Biology, focuses on publishing crucial advances in chemical biology research with broad appeal to our diverse community, spanning basic scientists to clinicians. Pioneering investigations at the chemistry-biology interface, the journal fosters collaboration between these disciplines. We encourage submissions providing significant conceptual advancements of broad interest across chemical, biological, clinical, and related fields. Particularly sought are articles utilizing chemical tools to perturb, visualize, and measure biological systems, offering unique insights into molecular mechanisms, disease biology, and therapeutics.
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