eprintid: 10163253 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/16/32/53 datestamp: 2023-01-17 16:44:33 lastmod: 2023-01-17 16:44:33 status_changed: 2023-01-17 16:44:33 type: article metadata_visibility: show sword_depositor: 699 creators_name: Fromentin, Sebastien creators_name: Forslund, Sofia K creators_name: Chechi, Kanta creators_name: Aron-Wisnewsky, Judith creators_name: Chakaroun, Rima creators_name: Nielsen, Trine creators_name: Tremaroli, Valentina creators_name: Ji, Boyang creators_name: Prifti, Edi creators_name: Myridakis, Antonis creators_name: Chilloux, Julien creators_name: Andrikopoulos, Petros creators_name: Fan, Yong creators_name: Olanipekun, Michael T creators_name: Alves, Renato creators_name: Adiouch, Solia creators_name: Bar, Noam creators_name: Talmor-Barkan, Yeela creators_name: Belda, Eugeni creators_name: Caesar, Robert creators_name: Coelho, Luis Pedro creators_name: Falony, Gwen creators_name: Fellahi, Soraya creators_name: Galan, Pilar creators_name: Galleron, Nathalie creators_name: Helft, Gerard creators_name: Hoyles, Lesley creators_name: Isnard, Richard creators_name: Le Chatelier, Emmanuelle creators_name: Julienne, Hanna creators_name: Olsson, Lisa creators_name: Pedersen, Helle Krogh creators_name: Pons, Nicolas creators_name: Quinquis, Benoit creators_name: Rouault, Christine creators_name: Roume, Hugo creators_name: Salem, Joe-Elie creators_name: Schmidt, Thomas SB creators_name: Vieira-Silva, Sara creators_name: Li, Peishun creators_name: Zimmermann-Kogadeeva, Maria creators_name: Lewinter, Christian creators_name: Sondertoft, Nadja B creators_name: Hansen, Tue H creators_name: Gauguier, Dominique creators_name: Gotze, Jens Peter creators_name: Kober, Lars creators_name: Kornowski, Ran creators_name: Vestergaard, Henrik creators_name: Hansen, Torben creators_name: Zucker, Jean-Daniel creators_name: Hercberg, Serge creators_name: Letunic, Ivica creators_name: Backhed, Fredrik creators_name: Oppert, Jean-Michel creators_name: Nielsen, Jens creators_name: Raes, Jeroen creators_name: Bork, Peer creators_name: Stumvoll, Michael creators_name: Segal, Eran creators_name: Clement, Karine creators_name: Dumas, Marc-Emmanuel creators_name: Ehrlich, S Dusko creators_name: Pedersen, Oluf title: Microbiome and metabolome features of the cardiometabolic disease spectrum ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F84 keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Medicine, Research & Experimental, Research & Experimental Medicine, CORONARY-ARTERY-DISEASE, GUT MICROBIOTA, P-CRESOL, HEART, RISK, IMPACT, SERUM, SIGNATURES, PLASMA, HEALTH note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ abstract: Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features. date: 2022-02-17 date_type: published publisher: NATURE PORTFOLIO official_url: https://doi.org/10.1038/s41591-022-01688-4 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1941668 doi: 10.1038/s41591-022-01688-4 medium: Print-Electronic pii: 10.1038/s41591-022-01688-4 lyricists_name: Ehrlich, Stanislav lyricists_id: SEHRL68 actors_name: Ehrlich, Stanislav actors_id: SEHRL68 actors_role: owner funding_acknowledgements: HEALTH-F4-2012-305312 [European Union]; ANR-11-DPBS-0001 [Metagenopolis grant]; [Leducq Foundation,]; [Novo Nordisk Foundation]; [NIHR Imperial Biomedical Research Centre]; ANR-10-LABX-46 [French National Research Agency]; ANR-18-IBHU-0001 [French National Agency for Research]; [European Union (FEDER)]; 20001891/NP0025517 [Hauts-de-France Regional Council]; 20002845 [Hauts-de-France Regional Council]; 2019_ESR_11 [European Metropolis of Lille]; ANR-16-IDEX-0004-ULNE [ANR]; [European Metropolis of Lille]; MR/S020039/1 [Medical Research Council Skills Development Fellowship]; 204834/Z/16/Z [Wellcome Trust]; MR/L01632X/1 [Medical Research Council Intermediate Research Fellowship in Data Science (UK Med-Bio)]; [German Centre for Cardiovascular Research]; SFB1365 [German Research Council]; SFB1470 [German Research Council]; KFO339 [German Research Council]; [German Ministry of Education and Research]; [National Center for Precision Diabetic Medicine] full_text_status: public publication: Nature Medicine volume: 28 number: 2 article_number: 303 pages: 31 event_location: United States citation: Fromentin, Sebastien; Forslund, Sofia K; Chechi, Kanta; Aron-Wisnewsky, Judith; Chakaroun, Rima; Nielsen, Trine; Tremaroli, Valentina; ... Pedersen, Oluf; + view all <#> Fromentin, Sebastien; Forslund, Sofia K; Chechi, Kanta; Aron-Wisnewsky, Judith; Chakaroun, Rima; Nielsen, Trine; Tremaroli, Valentina; Ji, Boyang; Prifti, Edi; Myridakis, Antonis; Chilloux, Julien; Andrikopoulos, Petros; Fan, Yong; Olanipekun, Michael T; Alves, Renato; Adiouch, Solia; Bar, Noam; Talmor-Barkan, Yeela; Belda, Eugeni; Caesar, Robert; Coelho, Luis Pedro; Falony, Gwen; Fellahi, Soraya; Galan, Pilar; Galleron, Nathalie; Helft, Gerard; Hoyles, Lesley; Isnard, Richard; Le Chatelier, Emmanuelle; Julienne, Hanna; Olsson, Lisa; Pedersen, Helle Krogh; Pons, Nicolas; Quinquis, Benoit; Rouault, Christine; Roume, Hugo; Salem, Joe-Elie; Schmidt, Thomas SB; Vieira-Silva, Sara; Li, Peishun; Zimmermann-Kogadeeva, Maria; Lewinter, Christian; Sondertoft, Nadja B; Hansen, Tue H; Gauguier, Dominique; Gotze, Jens Peter; Kober, Lars; Kornowski, Ran; Vestergaard, Henrik; Hansen, Torben; Zucker, Jean-Daniel; Hercberg, Serge; Letunic, Ivica; Backhed, Fredrik; Oppert, Jean-Michel; Nielsen, Jens; Raes, Jeroen; Bork, Peer; Stumvoll, Michael; Segal, Eran; Clement, Karine; Dumas, Marc-Emmanuel; Ehrlich, S Dusko; Pedersen, Oluf; - view fewer <#> (2022) Microbiome and metabolome features of the cardiometabolic disease spectrum. Nature Medicine , 28 (2) , Article 303. 10.1038/s41591-022-01688-4 <https://doi.org/10.1038/s41591-022-01688-4>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10163253/1/Microbiome%20and%20metabolome%20features%20of%20the%20cardiometabolic%20disease%20spectrum.pdf