Comprehensive metabolic profiling of Parkinson’s disease by liquid chromatography-mass spectrometry
Open accessAbstract
Background: Parkinson’s disease (PD) is a prevalent neurological disease in the elderly with increasing morbidity and mortality. Despite enormous efforts, rapid and accurate diagnosis of PD is still compromised. Metabolomics defines the final readout of genome-environment interactions through the analysis of the entire metabolic profile in biological matrices. Recently, unbiased metabolic profiling of human sample has been initiated to identify novel PD metabolic biomarkers and dysfunctional metabolic pathways, however, it remains a challenge to define reliable biomarker(s) for clinical use. Methods: We presented a comprehensive metabolic evaluation for identifying crucial metabolic disturbances in PD using liquid chromatography-high resolution mass spectrometry-based metabolomics approach. Plasma samples from 3 independent cohorts (n = 460, 223 PD, 169 healthy controls (HCs) and 68 PD-unrelated neurological disease controls) were collected for the characterization of metabolic changes resulted from PD, antiparkinsonian treatment and potential interferences of other diseases. Unbiased multivariate and univariate analyses were performed to determine the most promising metabolic signatures from all metabolomic datasets. Multiple linear regressions were applied to investigate the associations of metabolites with age, duration time and stage of PD. The combinational biomarker model established by binary logistic regression analysis was validated by 3 cohorts. Results: A list of metabolites including amino acids, acylcarnitines, organic acids, steroids, amides, and lipids from human plasma of 3 cohorts were identified. Compared with HC, we observed significant reductions of fatty acids (FFAs) and caffeine metabolites, elevations of bile acids and microbiota-derived deleterious metabolites, and alterations in steroid hormones in drug-naïve PD. Additionally, we found that L-dopa treatment could affect plasma metabolome involved in phenylalanine and tyrosine metabolism and alleviate the elevations of bile acids in PD. Finally, a metabolite panel of 4 biomarker candidates, including FFA 10:0, FFA 12:0, indolelactic acid and phenylacetyl-glutamine was identified based on comprehensive discovery and validation workflow. This panel showed favorable discriminating power for PD. Conclusions: This study may help improve our understanding of PD etiopathogenesis and facilitate target screening for therapeutic intervention. The metabolite panel identified in this study may provide novel approach for the clinical diagnosis of PD in the future.
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PD patients exhibit reduced plasma levels of the neuroprotective bile acids UDCA and TUDCA.
“Moreover, PD patients exhibited reduced plasma levels of neuroprotective BAs, namely UDCA and TUDCA.379”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [379]
Another study reports increased levels of glycine- and taurine-conjugated primary bile acids in plasma samples of PD patients.
“However, another study reported increased levels of glycine- and taurine-conjugated primary BAs in plasma samples of PD patients.379”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [379]
An elevated level of primary bile acid cholic acid is identified in the plasma of PD patients.
“An elevated level of primary BA (cholic acid) was identified in the plasma of PD patients.379,380”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [379]
Elevated levels of secondary bile acids are found in PD patients, while findings regarding primary bile acids have yielded varying results.
“Studies have revealed elevated levels of secondary BAs in PD patients, while findings regarding primary BAs have yielded varying results.377–380”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [379]
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The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases
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Lipid pathway dysfunction is prevalent in patients with Parkinson’s disease
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Lipoproteins in the Central Nervous System: From Biology to Pathobiology
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Mitochondrial complex I deficiency stratifies idiopathic Parkinson’s disease
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Polystyrene Nanoplastics Hitch-Hike the Gut–Brain Axis to Exacerbate Parkinson’s Pathology
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Multiomics Implicate Gut Microbiota in Altered Lipid and Energy Metabolism in Parkinson’s Disease
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New Understanding on the Pathophysiology and Treatment of Constipation in Parkinson’s Disease
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Amyloid Fibers of α-Synuclein Catalyze Chemical Reactions
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Emerging Roles of Bile Acids in Neuroinflammation
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Hot Topics in Recent Parkinson’s Disease Research: Where We are and Where We Should Go
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Omics data integration suggests a potential idiopathic Parkinson’s disease signature
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Metabolomics in Parkinson’s Disease and Correlation with Disease State
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Metabolomics Unveils Disrupted Pathways in Parkinson’s Disease: Toward Biomarker-Based Diagnosis
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Cerebral venous congestion alters brain metabolite profiles, impairing cognitive function
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Metabolomics of blood reveals age-dependent pathways in Parkinson’s Disease
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Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites
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α-synuclein overexpression and the microbiome shape the gut and brain metabolome in mice
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The Role of an Altered Gut Microbiome in Parkinson’s Disease: A Narrative Review
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Bile acid metabolism is altered in learning and memory impairment induced by chronic lead exposure
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Pursuing Multiple Biomarkers for Early Idiopathic Parkinson’s Disease Diagnosis
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Metabolic modeling links gut microbiota to metabolic markers of Parkinson’s disease
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Plasma Metabolite Signature Classifies Male LRRK2 Parkinson’s Disease Patients
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Identification of gut metabolites associated with Parkinson’s disease using bioinformatic analyses
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The molecular insights of bile acid homeostasis in host diseases
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A Review on Differential Abundance Analysis Methods for Mass Spectrometry-Based Metabolomic Data
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Analysis of circulating metabolites to differentiate Parkinson’s disease and essential tremor
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What Dietary Vitamins and Minerals Might Be Protective against Parkinson’s Disease?
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Integrated metabolomics and proteomics analysis of plasma lipid metabolism in Parkinson’s disease
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Does Bisphenol A (BPA) Exposure Cause Human Diseases?
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Serum neurotransmitter analysis of motor and non-motor symptoms in Parkinson’s patients
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Self-citationEvaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders
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Variations in the oral microbiome and metabolome of methamphetamine users
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- Authors
- Shao, Y., Li, T., Liu, Z., Wang, X., Xu, X., Li, S., Xu, G., & Le, W.
- Affiliations
- Dalian Medical University (CN)
- Dalian Institute of Chemical Physics (CN)
- University of Electronic Science and Technology of China (CN)
- Corresponding author
- Xu, Guowang
- Le, Weidong
- Venue
- Molecular Neurodegeneration
- Published
- 2021-01-23
- Volume
- 16
- Issue
- 1
- Pages
- 4-4
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC7825156
- OpenAlex
- W3125488374
- Cited by
- 226
- References
- 83
- Citations by year
- 2026: 37 · 2025: 57 · 2024: 56 · 2023: 36 · 2022: 27 · 2021: 11 · 2019: 1
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Program of China (2016YFC1306600)
- National Natural Science Foundation of China (81771521, 21876169, 22004013)
- Key Realm R&D Program of Guangdong Province (2018B030337001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- Parkinson's disease, plasma metabolomics, metabolic biomarkers, diagnostic biomarker panel, fatty acids, bile acids, L-dopa treatment, phenylalanine and tyrosine metabolism, caffeine metabolites, gut microbiota metabolites, steroid hormones, indolelactic acid, Parkinson's disease diagnosis
- MeSH terms
- Aged, Chromatography, Liquid, Female, Humans, Male, Parkinson Disease, Mass Spectrometry, Biomarkers, Case-Control Studies, Metabolomics, Metabolome
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