Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan.
Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung 40402, Taiwan.
Int J Mol Sci. 2020 Apr 11;21(8):2676. doi: 10.3390/ijms21082676.
An increasing number of studies have shown that the brain-gut-microbiota axis may significantly contribute to Alzheimer's disease (AD) pathogenesis. Moreover, impaired memory and learning involve the dysfunction neurotransmission of glutamate, the agonist of the -methyl-d-aspartate receptor and a major excitatory neurotransmitter in the brain. This systematic review aimed to summarize the current cutting-edge research on the gut microbiota and glutamate alterations associated with dementia.
PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews were reviewed for all studies on glutamate and gut microbiota in dementia published up until Feb 2020.
Several pilot studies have reported alterations of gut microbiota and metabolites in AD patients and other forms of dementia. Gut microbiota including and affect glutamate metabolism and decrease the glutamate metabolite 2-keto-glutaramic acid. Meanwhile, gut bacteria with glutamate racemase including , and can convert l-glutamate to d-glutamate. N-methyl-d-aspartate glutamate receptor (NMDAR)-enhancing agents have been found to potentially improve cognition in AD or Parkinson's disease patients. These findings suggest that d-glutamate (d-form glutamate) metabolized by the gut bacteria may influence the glutamate NMDAR and cognitive function in dementia patients.
Gut microbiota and glutamate are potential novel interventions to be developed for dementia. Exploring comprehensive cognitive functions in animal and human trials with glutamate-related NMDAR enhancers are warranted to examine d-glutamate signaling efficacy in gut microbiota in patients with AD and other neurodegenerative dementias.
越来越多的研究表明，脑-肠-微生物群轴可能对阿尔茨海默病（AD）的发病机制有重要贡献。此外，记忆和学习受损涉及谷氨酸能神经传递功能障碍，谷氨酸是 -甲基-D-天冬氨酸受体的激动剂，也是大脑中的主要兴奋性神经递质。本系统综述旨在总结与痴呆相关的肠道微生物群和谷氨酸改变的最新前沿研究。
检索了PubMed、Cochrane 协作中心对照临床试验注册库和 Cochrane 系统评价数据库，以获取截至 2020 年 2 月发表的关于痴呆症中谷氨酸和肠道微生物群的所有研究。
几项初步研究报告了 AD 患者和其他形式痴呆症患者肠道微生物群和代谢物的改变。肠道微生物群包括 和 会影响谷氨酸代谢并降低谷氨酸代谢物 2-酮戊二酸。同时，具有谷氨酸消旋酶的肠道细菌包括 、 和 可以将 l-谷氨酸转化为 d-谷氨酸。已发现 N-甲基-D-天冬氨酸谷氨酸受体（NMDAR）增强剂可能潜在改善 AD 或帕金森病患者的认知功能。这些发现表明，由肠道细菌代谢的 d-谷氨酸（d-形式谷氨酸）可能会影响痴呆症患者的谷氨酸 NMDAR 和认知功能。
肠道微生物群和谷氨酸可能是痴呆症的潜在新干预措施。在动物和人类试验中，用与谷氨酸相关的 NMDAR 增强剂来探索全面的认知功能，以检验 AD 和其他神经退行性痴呆患者中肠道微生物群中 d-谷氨酸信号转导的疗效是必要的。
