Article (Scientific journals)
Integrated Analyses of Microbiome and Longitudinal Metabolome Data Reveal Microbial-Host Interactions on Sulfur Metabolism in Parkinson’s Disease
Hertel, Johannes; Harms, Amy C.; Heinken, Almut et al.
2019In Cell Reports, 29 (7), p. 1767-1777
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Keywords :
Parkinson's disease; metabolomics; analysis; statistics; constraint-based modeling; gut microbiome; metabolism; computational modeling; prediction
Abstract :
[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
Hankemeier, Thomas
Fleming, Ronan M.T.
Mollenhauer, Brit
Thiele, Ines
More authors (7 more) Less
External co-authors :
yes
Language :
English
Title :
Integrated Analyses of Microbiome and Longitudinal Metabolome Data Reveal Microbial-Host Interactions on Sulfur Metabolism in Parkinson’s Disease
Publication date :
2019
Journal title :
Cell Reports
eISSN :
2211-1247
Publisher :
Elsevier, Amsterdam, Netherlands
Volume :
29
Issue :
7
Pages :
1767-1777
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
European Projects :
H2020 - 757922 - BugTheDrug - Predicting the effects of gut microbiota and diet on an individual’s drug response and safety
FnR Project :
FNR11264123 - Ncer-pd, 2015 (01/01/2015-30/11/2020) - Rejko Krüger
Name of the research project :
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
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since 10 October 2019

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