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

Published version
Peer-reviewed

Type

Article

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Authors

Hertel, Johannes 
Harms, Amy C 
Heinken, Almut 
Baldini, Federico 
Thinnes, Cyrille C 

Abstract

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.

Description

Keywords

Parkinson's disease, bile acid metabolism, metabolic modeling, metabolism, metabolomics, metagenomics, microbiome, neurodegenerative disease, taurine metabolism, transsulfuration pathway, Aged, Female, Gastrointestinal Microbiome, Humans, Longitudinal Studies, Male, Middle Aged, Parkinson Disease, Sulfur

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

29

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MC_UU_12015/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Medical Research Council (MR/N003284/1)
Medical Research Council (G1000143)
Medical Research Council (G0401527)
Medical Research Council (G0401527/1)
Cancer Research Uk (None)