Next Article in Journal
HPV Infection Significantly Accelerates Glycogen Metabolism in Cervical Cells with Large Nuclei: Raman Microscopic Study with Subcellular Resolution
Next Article in Special Issue
Structural Changes in Hippocampal Subfields in Patients with Continuous Remission of Drug-Naive Major Depressive Disorder
Previous Article in Journal
Evaluation of Salivary Cytokines and Vitamin D Levels in Periodontopathic Patients
Previous Article in Special Issue
Neuroimaging Biomarkers for Predicting Treatment Response and Recurrence of Major Depressive Disorder
Open AccessReview

d-glutamate and Gut Microbiota in Alzheimer’s Disease

by Chun-Hung Chang 1,2,3, Chieh-Hsin Lin 1,4,5,6,* and Hsien-Yuan Lane 1,2,4,7,*
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;
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. View Full-Text
Keywords: Glutamate; gut microbiota; dementia; brain–gut–microbiota axis; Alzheimer’s disease; N-methyl-d-aspartate glutamate receptor Glutamate; gut microbiota; dementia; brain–gut–microbiota axis; Alzheimer’s disease; N-methyl-d-aspartate glutamate receptor
Show Figures

Figure 1

MDPI and ACS Style

Chang, C.-H.; Lin, C.-H.; Lane, H.-Y. d-glutamate and Gut Microbiota in Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 2676.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Search more from Scilit
Back to TopTop