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dc.contributor.authorHertel, Johannes
dc.contributor.authorHarms, Amy C.
dc.contributor.authorHeinken, Almut
dc.contributor.authorBaldini, Federico
dc.contributor.authorThinnes, Cyrille C
dc.contributor.authorGlaab, Enrico
dc.contributor.authorVasco, Daniel A.
dc.contributor.authorPietzner, Maik
dc.contributor.authorStewart, Isobel D.
dc.contributor.authorWareham, Nicholas J.
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorTrenkwalder, Claudia
dc.contributor.authorKrüger, Rejko
dc.contributor.authorHankemeier, Thomas
dc.contributor.authorFleming, Ronan M. T.
dc.contributor.authorMollenhauer, Brit
dc.contributor.authorThiele, Ines
dc.date.accessioned2019-11-19T15:20:11Z
dc.date.available2019-11-19T15:20:11Z
dc.date.issued2019-11-12
dc.identifier.citationHertel, Johannes, Harms, Amy C., Heinken, Almut, Baldini, Federico, Thinnes, Cyrille C., Glaab, Enrico, Vasco, Daniel A., Pietzner, Maik, Stewart, Isobel D.,Wareham, Nicholas J.,Langenberg, Claudia, Trenkwalder, Claudia, Krüger, Rejko, Hankemeier, Thomas, Fleming, Ronan M. T., Mollenhauer, Brit, Thiele, Ines. (2019). Integrated Analyses of Microbiome and Longitudinal Metabolome Data Reveal Microbial-Host Interactions on Sulfur Metabolism in Parkinson’s Disease. Cell Reports, 29(7), 1767-1777.e1768. doi: https://doi.org/10.1016/j.celrep.2019.10.035en_IE
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/10379/15580
dc.description.abstractParkinson'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.en_IE
dc.description.sponsorshipThis study was funded by Luxembourg National Research Fund (FNR) through the ATTRACT programme grant (FNR/A12/01 to I.T.), the National Centre of Excellence in Research (NCER) on Parkinson’s disease, and by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 757922). The EPIC-Norfolk study (https://doi.org/10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). Metabolite measurements in the EPIC-Norfolk study were supported by the MRC Cambridge Initiative in Metabolic Science (MR/L00002/1) and the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372.en_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofCell Reportsen
dc.subjectmetabolismen_IE
dc.subjectParkinson's diseaseen_IE
dc.subjectneurodegenerative diseaseen_IE
dc.subjectpathwayen_IE
dc.subjectmetabolomicsen_IE
dc.subjectmetagenomicsen_IE
dc.subjectmetabolicen_IE
dc.subjectmodelingen_IE
dc.subjecttaurineen_IE
dc.subjectmetabolismen_IE
dc.subjectbile acid metabolismen_IE
dc.subjectmicrobiomeen_IE
dc.subjecttranssulfuration pathwayen_IE
dc.titleIntegrated analyses of microbiome and longitudinal metabolome data reveal microbial-host interactions on sulfur metabolism in Parkinson's disease.en_IE
dc.typeArticleen_IE
dc.date.updated2019-11-18T22:39:54Z
dc.identifier.doi10.1016/j.celrep.2019.10.035
dc.local.publishedsourcehttps://doi.org/10.1016/j.celrep.2019.10.035en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderFonds National de la Recherche Luxembourgen_IE
dc.contributor.funderNational Centre of Excellence in Research (NCER)en_IE
dc.contributor.funderEuropean Research Councilen_IE
dc.contributor.funderHorizon 2020en_IE
dc.contributor.funderMedical Research Councilen_IE
dc.contributor.funderCancer Research UKen_IE
dc.internal.rssid18493437
dc.local.contactInes Thiele. Email: ines.thiele@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionPUBLISHED
dcterms.projectinfo:eu-repo/grantAgreement/EC/H2020::ERC::ERC-STG/757922/EU/Predicting the effects of gut microbiota and diet on an individual’s drug response and safety/BugTheDrugen_IE
dcterms.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::SP1-JTI/115372/EU/European Medical Information Framework/EMIFen_IE
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