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Integrated Analyses of Microbiome and Longitudinal Metabolome Data Reveal Microbial-Host Interactions on Sulfur Metabolism in Parkinson's Disease

37 Pages Posted: 26 Feb 2019 Sneak Peek Status: Review Complete

See all articles by Johannes Hertel

Johannes Hertel

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine; University of Greifswald, University Medicine Greifswald, Department of Psychiatry and Psychotherapy

Amy C. Harms

Leiden University, Faculty of Science, Leiden Academic Centre for Drug Research, Division of Systems Biomedicine and Pharmacology

Almut Heinken

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Federico Baldini

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Cyrille C. Thinnes

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Enrico Glaab

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Daniel A. Vasco

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Claudia Trenkwalder

Paracelsus-Elena-Klinik; University of Goettingen (Gottingen), Faculty of Medicine, University Medical Centre, Department of Neurosurgery

Rejko Krüger

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Thomas Hankemeier

Leiden University, Faculty of Science, Leiden Academic Centre for Drug Research, Division of Systems Biomedicine and Pharmacology

Ronan M. T. Fleming

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine; Leiden University, Faculty of Science, Leiden Academic Centre for Drug Research, Division of Systems Biomedicine and Pharmacology

Brit Mollenhauer

Paracelsus-Elena-Klinik; University of Goettingen (Gottingen), Faculty of Medicine, University Medical Centre, Department of Neurology

Ines Thiele

Universite du Luxembourg, Luxembourg Centre for Systems Biomedicine

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Abstract

Parkinson’s disease (PD) exhibits systemic effects on human metabolism with emerging roles for the gut microbiome. Here, we integrate longitudinal metabolome data from 30 drug-naïve, de-novo PD patients and 30 matched controls with constraint-based modeling of gut microbial communities derived from an independent, drug-naïve PD cohort. Our key results are i) metabolites associated with the interconversion of methionine and cysteine via cystathionine differed strongly in their longitudinal trajectory between PD patients and controls, ii) dopaminergic medication showed strong lipidomic signatures, iii) histidine and taurine-conjugated bile acids correlated with the severity of motor symptoms, with low baseline histidine levels being predictive for faster disease progression, and iv) computational modeling predicted changes in microbial sulfur metabolism, driven by A. muciniphila and B. wadsworthia, and consistent with the changed metabolome. In conclusion, the integration of metabolomic and metagenomic data revealed substantial PD-specific patterns in microbial-host sulfur metabolism that may contribute to PD’s severity.

Suggested Citation

Hertel, Johannes and Harms, Amy C. and Heinken, Almut and Baldini, Federico and Thinnes, Cyrille C. and Glaab, Enrico and Vasco, Daniel A. and Trenkwalder, Claudia and Krüger, Rejko and Hankemeier, Thomas and Fleming, Ronan M. T. and Mollenhauer, Brit and Thiele, Ines, Integrated Analyses of Microbiome and Longitudinal Metabolome Data Reveal Microbial-Host Interactions on Sulfur Metabolism in Parkinson's Disease. Available at SSRN: https://ssrn.com/abstract=3305554 or http://dx.doi.org/10.2139/ssrn.3305554
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Johannes Hertel

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Campus Belval
Esch-sur-Alzette
Luxembourg

University of Greifswald, University Medicine Greifswald, Department of Psychiatry and Psychotherapy

Greifswald
Germany

Amy C. Harms

Leiden University, Faculty of Science, Leiden Academic Centre for Drug Research, Division of Systems Biomedicine and Pharmacology

Netherlands

Almut Heinken

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Federico Baldini

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Cyrille C. Thinnes

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Enrico Glaab

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Daniel A. Vasco

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Claudia Trenkwalder

Paracelsus-Elena-Klinik

Kassel, 34128
Germany

University of Goettingen (Gottingen), Faculty of Medicine, University Medical Centre, Department of Neurosurgery

Goettingen
Germany

Rejko Krüger

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Thomas Hankemeier

Leiden University, Faculty of Science, Leiden Academic Centre for Drug Research, Division of Systems Biomedicine and Pharmacology

Netherlands

Ronan M. T. Fleming

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Leiden University, Faculty of Science, Leiden Academic Centre for Drug Research, Division of Systems Biomedicine and Pharmacology

Netherlands

Brit Mollenhauer

Paracelsus-Elena-Klinik

Kassel, 34128
Germany

University of Goettingen (Gottingen), Faculty of Medicine, University Medical Centre, Department of Neurology

Goettingen
Germany

Ines Thiele (Contact Author)

Universite du Luxembourg, Luxembourg Centre for Systems Biomedicine ( email )

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

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