d-glutamate and Gut Microbiota in Alzheimer’s Disease
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
An Nan Hospital, China Medical University, Tainan 709025, Taiwan
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung 41354, Taiwan
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2676; https://doi.org/10.3390/ijms21082676
Received: 3 April 2020 / Accepted: 9 April 2020 / Published: 11 April 2020
(This article belongs to the Special Issue Biomarkers Guided Diagnosis and Therapy: Toward Precision Psychiatry)
Background: 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 N-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. Methods: 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. Results: Several pilot studies have reported alterations of gut microbiota and metabolites in AD patients and other forms of dementia. Gut microbiota including Bacteroides vulgatus and Campylobacter jejuni affect glutamate metabolism and decrease the glutamate metabolite 2-keto-glutaramic acid. Meanwhile, gut bacteria with glutamate racemase including Corynebacterium glutamicum, Brevibacterium lactofermentum, and Brevibacterium avium 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. Conclusions: 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.