Integrated Analyses of Microbiome and Longitudinal Metabolome Data Reveal Microbial-Host Interactions on Sulfur Metabolism in Parkinson’s Disease
Open accessAbstract
Parkinson's disease (PD) exhibits systemic effects on the human metabolism, with emerging roles for the gut microbiome. Here, we integrate longitudinal metabolome data from 30 drug-naive, de novo PD patients and 30 matched controls with constraint-based modeling of gut microbial communities derived from an independent, drug-naive PD cohort, and prospective data from the general population. Our key results are (1) longitudinal trajectory of metabolites associated with the interconversion of methionine and cysteine via cystathionine differed between PD patients and controls; (2) dopaminergic medication showed strong lipidomic signatures; (3) taurine-conjugated bile acids correlated with the severity of motor symptoms, while low levels of sulfated taurolithocholate were associated with PD incidence in the general population; and (4) computational modeling predicted changes in sulfur metabolism, driven by A. muciniphila and B. wadsworthia, which is consistent with the changed metabolome. The multi-omics integration reveals PD-specific patterns in microbial-host sulfur co-metabolism that may contribute to PD severity.
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Because of dysbiosis, lipid, amino acid and energy metabolism are often dysregulated in Parkinson's disease patients.
“because of dysbiosis, lipid, amino acid and energy metabolism are often dysregulated in PD patients [96,97,98,99,100]”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [96]
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- Authors
- Hertel, J., Harms, A. C., Heinken, A., Baldini, F., Thinnes, C. C., Glaab, E., Vasco, D. A., Pietzner, M., Stewart, I. D., Wareham, N. J., Langenberg, C., Trenkwalder, C., Krüger, R., Hankemeier, T., Fleming, R. M. T., Mollenhauer, B., & Thiele, I.
- Affiliations
- University of Luxembourg (LU)
- Leiden University (NL)
- University of Cambridge (GB)
- Universitätsmedizin Göttingen (DE)
- Centre Hospitalier de Luxembourg (LU)
- Corresponding author
- Thiele, Ines
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 29
- Issue
- 7
- Pages
- 1767-1777.e8
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6856723
- OpenAlex
- W2981449190
- Cited by
- 162
- References
- 76
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 24 · 2023: 28 · 2022: 35 · 2021: 25 · 2020: 11
- FWCI
- 5.84
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- journal article
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- en
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- gold
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- Apollo (cc-by)
- Funders
- European Research Council
- Fonds National de la Recherche Luxembourg
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- Parkinson's disease, gut microbiota, sulfur metabolism, cystathionine, bile acids, taurine-conjugated bile acids, taurolithocholate, dopaminergic therapy, lipidomics, Akkermansia muciniphila, host-microbe interactions, motor impairment severity, multi-omics integration, constraint-based modeling
- MeSH terms
- Gastrointestinal Microbiome, Aged, Female, Humans, Longitudinal Studies, Male, Middle Aged, Parkinson Disease, Sulfur
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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