dc.contributor.author | Hertel, Johannes | |
dc.contributor.author | Harms, Amy C. | |
dc.contributor.author | Heinken, Almut | |
dc.contributor.author | Baldini, Federico | |
dc.contributor.author | Thinnes, Cyrille C | |
dc.contributor.author | Glaab, Enrico | |
dc.contributor.author | Vasco, Daniel A. | |
dc.contributor.author | Pietzner, Maik | |
dc.contributor.author | Stewart, Isobel D. | |
dc.contributor.author | Wareham, Nicholas J. | |
dc.contributor.author | Langenberg, Claudia | |
dc.contributor.author | Trenkwalder, Claudia | |
dc.contributor.author | Krüger, Rejko | |
dc.contributor.author | Hankemeier, Thomas | |
dc.contributor.author | Fleming, Ronan M. T. | |
dc.contributor.author | Mollenhauer, Brit | |
dc.contributor.author | Thiele, Ines | |
dc.date.accessioned | 2019-11-19T15:20:11Z | |
dc.date.available | 2019-11-19T15:20:11Z | |
dc.date.issued | 2019-11-12 | |
dc.identifier.citation | Hertel, 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.2019.10.035 | en_IE |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/10379/15580 | |
dc.description.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. | en_IE |
dc.description.sponsorship | This 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.iso | en | en_IE |
dc.publisher | Elsevier | en_IE |
dc.relation.ispartof | Cell Reports | en |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | metabolism | en_IE |
dc.subject | Parkinson's disease | en_IE |
dc.subject | neurodegenerative disease | en_IE |
dc.subject | pathway | en_IE |
dc.subject | metabolomics | en_IE |
dc.subject | metagenomics | en_IE |
dc.subject | metabolic | en_IE |
dc.subject | modeling | en_IE |
dc.subject | taurine | en_IE |
dc.subject | metabolism | en_IE |
dc.subject | bile acid metabolism | en_IE |
dc.subject | microbiome | en_IE |
dc.subject | transsulfuration pathway | en_IE |
dc.title | Integrated analyses of microbiome and longitudinal metabolome data reveal microbial-host interactions on sulfur metabolism in Parkinson's disease. | en_IE |
dc.type | Article | en_IE |
dc.date.updated | 2019-11-18T22:39:54Z | |
dc.identifier.doi | 10.1016/j.celrep.2019.10.035 | |
dc.local.publishedsource | https://doi.org/10.1016/j.celrep.2019.10.035 | en_IE |
dc.description.peer-reviewed | peer-reviewed | |
dc.contributor.funder | Fonds National de la Recherche Luxembourg | en_IE |
dc.contributor.funder | National Centre of Excellence in Research (NCER) | en_IE |
dc.contributor.funder | European Research Council | en_IE |
dc.contributor.funder | Horizon 2020 | en_IE |
dc.contributor.funder | Medical Research Council | en_IE |
dc.contributor.funder | Cancer Research UK | en_IE |
dc.internal.rssid | 18493437 | |
dc.local.contact | Ines Thiele. Email: ines.thiele@nuigalway.ie | |
dc.local.copyrightchecked | Yes | |
dc.local.version | PUBLISHED | |
dcterms.project | info: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/BugTheDrug | en_IE |
dcterms.project | info:eu-repo/grantAgreement/EC/FP7::SP1::SP1-JTI/115372/EU/European Medical Information Framework/EMIF | en_IE |
nui.item.downloads | 333 | |