Gut microbial metabolites in Parkinson's disease: Association with lifestyle, disease characteristics, and treatment status
Open accessAbstract
There is growing appreciation of the importance of the intestinal microbiota in Parkinson's disease (PD), and one potential mechanism by which the intestinal microbiota can communicate with the brain is via bacteria-derived metabolites. In this study, plasma levels of bacterial-derived metabolites including trimethylamine-N-oxide (TMAO), short chain fatty acids (SCFA), the branched chain fatty acid isovalerate, succinate, and lactate were evaluated in PD subjects (treatment naïve and treated) which were compared to (1) population controls, (2) spousal / household controls (similar lifestyle to PD subjects), and (3) subjects with multiple system atrophy (MSA). Analyses revealed an increase in the TMAO pathway in PD subjects which was independent of medication status, disease characteristics, and lifestyle. Lactic acid was decreased in treated PD subjects, succinic acid positively correlated with disease severity, and the ratio of pro-inflammatory TMAO to the putative anti-inflammatory metabolite butyric acid was significantly higher in PD subjects compared to controls indicating a pro-inflammatory shift in the metabolite profile in PD subjects. Finally, acetic and butyric acid were different between PD and MSA subjects indicating that metabolites may differentiate these synucleinopathies. In summary, (1) TMAO is elevated in PD subjects, a phenomenon independent of disease characteristics, treatment status, and lifestyle and (2) metabolites may differentiate PD and MSA subjects. Additional studies to understand the potential of TMAO and other bacterial metabolites to serve as a biomarker or therapeutic targets are warranted.
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Elevated levels of TMAO have been reported in the plasma and CSF of individuals with MCI, AD, and PD.
“Studies have reported elevated levels of TMAO in the plasma and CSF of individuals with MCI, AD, and PD.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [667]
Trimethylamine-N-oxide may enhance inflammation and oxidative stress.
“trimethylamine-N-oxide may enhance inflammation and oxidative stress [68]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [68]
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3 of the 108 references couldn’t be matched to a known paper.
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Buty and the beast: the complex role of butyrate in Parkinson’s disease
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The Intricate Interplay: Microbial Metabolites and the Gut‐Liver‐Brain Axis in Parkinson's Disease
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The role of the gut microbiota in neuropsychiatric disorders and therapy
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The Enteric Nervous System as a Mediator of Microbiota‐Gut‐Brain Interactions in Parkinson's Disease
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Alterations of Gut Microbiota and Microbial Metabolites in Parkinson’s Disease: A Systematic Review
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Metabolic profiles associated with fat loss in Parkinson’s disease
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- Authors
- Voigt, R. M., Wang, Z., Brown, J. M., Engen, P. A., Naqib, A., Goetz, C. G., Hall, D. A., Metman, L. V., Shaikh, M., Forsyth, C. B., & Keshavarzian, A.
- Affiliations
- Rush University Medical Center (US)
- Cleveland Clinic (US)
- Corresponding author
- Voigt, Robin M.
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 170
- Pages
- 105780
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC9241494
- OpenAlex
- W4281782870
- Cited by
- 51
- References
- 108
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 11 · 2023: 11 · 2022: 3
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Cleveland Clinic
- National Institutes of Health (AA026801)
- National Institute on Alcohol Abuse and Alcoholism (AA024333, AA026801, P50AA024333, R24AA026801)
- National Institute on Aging (AG056653, R01AG056653)
- National Heart, Lung, and Blood Institute (P01HL147823, R01HL130819)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK120679, DK130227, R01DK130227)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Parkinson's disease, gut microbiota, bacterial metabolites, trimethylamine N-oxide, short-chain fatty acids, isovalerate, succinic acid, lactate, butyrate, multiple system atrophy, synucleinopathies, inflammation, biomarkers
- MeSH terms
- Gastrointestinal Microbiome, Bacteria, Butyrates, Humans, Life Style, Parkinson Disease, Multiple System Atrophy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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