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d-glutamate and Gut Microbiota in Alzheimer’s Disease
Open accessAbstract
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.
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“glutamate does not readily cross the BBB, which may limit its direct influence on brain glutamate levels.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [541]
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Self-citation
Metadata
- Authors
- Chang, C.-H., Lin, C.-H., & Lane, H.-Y.
- Affiliations
- China Medical University (TW)
- Chang Gung University (TW)
- Asia University (TW)
- Corresponding author
- Lin, Chieh-Hsin
- Lane, Hsien-Yuan
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-04-11
- Volume
- 21
- Issue
- 8
- Pages
- 2676
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7215955
- OpenAlex
- W3015756776
- Cited by
- 191
- References
- 132
- Citations by year
- 2026: 14 · 2025: 40 · 2024: 47 · 2023: 31 · 2022: 32 · 2021: 19 · 2020: 8
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- China Medical University Hospital (DMR‐108‐BC2)
- Chang Gung Medical Foundation
- Ministry of Science and Technology, Taiwan (MOST108-2628-B182A-002, MOST108-2314-B039-002, MOST107-2628-B182A-002, MOST107-2632-B039-001)
- National Health Research Institutes (NHRI-EX108-10731NI)
- China Medical University
- Division of Materials Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- D-glutamic acid, gut microbiota, Alzheimer's disease, dementia, brain-gut-microbiota axis, glutamate metabolism, NMDA receptor, glutamate racemase, Bacteroides vulgatus, Campylobacter jejuni, Corynebacterium glutamicum, Brevibacterium lactofermentum, cognitive function, neurodegenerative diseases, Parkinson's disease
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Animals, Blood-Brain Barrier, Brain, Diet, Disease Susceptibility, Humans, Synaptic Transmission, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Glutamic Acid, Metabolic Networks and Pathways
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