[en] Parkinson’s disease (PD) exhibits systemic effects on human metabolism with emerging roles for the gut microbiome. Here, we integrated 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, and prospective data from a general population. Our key results are i) longitudinal trajectory of metabolites associated with the interconversion of methionine and cysteine via cystathionine differed between PD patients and controls, ii) dopaminergic medication showed strong lipidomic signatures, iii) taurine-conjugated bile acids correlated with the severity of motor symptoms, while low levels of sulfated taurolithocholate were associated with incident PD in the general population, and iv) computational modeling predicted changes in sulfur metabolism, driven by A. muciniphila and B. wadsworthia, consistent with the changed metabolome. In conclusion, the multi-omics integration revealed PD-specific patterns in microbial-host sulfur co-metabolism that may contribute to PD severity.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB)
Disciplines :
Human health sciences: Multidisciplinary, general & others Biotechnology Life sciences: Multidisciplinary, general & others Neurology
Author, co-author :
Hertel, Johannes
Harms, Amy C.
Heinken, Almut
BALDINI, Federico ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Thinnes, Cyrille C.
GLAAB, Enrico ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Vasco, Daniel
Pietzner, Maik
Stewart, Isobel D.
Wareham, Nicholas J.
Langenberg, Claudia
Trenkwalder, Claudia
KRÜGER, Rejko ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
National Centre of Excellence in Research (NCER) on Parkinson’s disease
Funders :
FNR - Fonds National de la Recherche CER - Conseil Européen de la Recherche MRC - Medical Research Council Cambridge Lipidomics Biomarker Research Initiative CE - Commission Européenne European Union