Microbiome and metabolome features of the cardiometabolic disease spectrum
Artikel i vetenskaplig tidskrift, 2022
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.
Författare
Sebastien Fromentin
Université Paris-Saclay
Sofia K. Forslund
European Molecular Biology Laboratory
Charité Universitätsmedizin Berlin
Max Delbrueck Centrum Fuer Molekulare Medizin
Deutsches Zentrum für Herz-Kreislauf-Forschung e. V.
Kanta Chechi
St Mary's Hospital
National Heart and Lung Institute
Department of Metabolism
Judith Aron-Wisnewsky
Sorbonne Université
Assistance publique – Hôpitaux de Paris (AP-HP)
Rima Chakaroun
Universität Leipzig
Trine Nielsen
Köpenhamns universitet
Valentina Tremaroli
Wallenberg Lab.
Boyang Ji
Chalmers, Biologi och bioteknik, Systembiologi
Edi Prifti
Sorbonne Université
UMMISCO
Antonis Myridakis
Department of Metabolism
J. Chilloux
Department of Metabolism
Petros Andrikopoulos
National Heart and Lung Institute
Department of Metabolism
Yong Fan
Köpenhamns universitet
Michael Olanipekun
Department of Metabolism
National Heart and Lung Institute
Renato Alves
European Molecular Biology Laboratory
Solia Adiouch
Sorbonne Université
Noam Bar
Weizmann Institute of Science
Yeela Talmor-Barkan
Rabin Medical Center Israel
Weizmann Institute of Science
Sackler Faculty of Medicine
Eugeni Belda
Assistance publique – Hôpitaux de Paris (AP-HP)
Sorbonne Université
Integrative Phenomics
Robert Caesar
Wallenberg Lab.
Luis P. Coelho
European Molecular Biology Laboratory
Gwen Falony
Flanders Interuniversity Institute for Biotechnology
KU Leuven
Soraya Fellahi
Hôpital Henri Mondor
Pilar Galan
Université Paris-Saclay
Nathalie Galleron
Université Paris-Saclay
Gerard Helft
Assistance publique – Hôpitaux de Paris (AP-HP)
L. Hoyles
Department of Metabolism
Nottingham Trent University
Richard Isnard
Assistance publique – Hôpitaux de Paris (AP-HP)
Emmanuelle Le Chatelier
Université Paris-Saclay
Hanna Julienne
Université Paris-Saclay
Lisa M. Olsson
Wallenberg Lab.
Helle K. Pedersen
Köpenhamns universitet
Nicolas Pons
Université Paris-Saclay
Benoit Quinquis
Université Paris-Saclay
Christine Rouault
Sorbonne Université
Hugo Roume
Université Paris-Saclay
Joe-Elie Salem
Sorbonne Université
Thomas S. B. Schmidt
European Molecular Biology Laboratory
Sara Vieira-Silva
KU Leuven
Flanders Interuniversity Institute for Biotechnology
Peishun Li
Chalmers, Biologi och bioteknik, Systembiologi
Maria Zimmermann-Kogadeeva
European Molecular Biology Laboratory
Christian Lewinter
Köpenhamns universitet
Nadja B. Søndertoft
Köpenhamns universitet
Tue H. Hansen
Köpenhamns universitet
Dominique Gauguier
Université Paris Descartes
Jens P. Gøtze
Köpenhamns universitet
Lars Køber
Köpenhamns universitet
Ran Kornowski
Rabin Medical Center Israel
H. Vestergaard
Bornholms Hospital
Köpenhamns universitet
Torben Hansen
Köpenhamns universitet
Jean-Daniel Zucker
UMMISCO
Sorbonne Université
Serge Hercberg
Université Paris Nord
Ivica Letunic
Biobyte Solutions
Fredrik Bäckhed
Köpenhamns universitet
Wallenberg Lab.
Jean-Michel Oppert
Assistance publique – Hôpitaux de Paris (AP-HP)
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
Jeroen Raes
Flanders Interuniversity Institute for Biotechnology
KU Leuven
Peer Bork
European Molecular Biology Laboratory
M. Stumvoll
Universität Leipzig
Eran Segal
Weizmann Institute of Science
K. Clement
Sorbonne Université
Assistance publique – Hôpitaux de Paris (AP-HP)
Marc-Emmanuel Dumas
CHU Lille
National Heart and Lung Institute
Department of Metabolism
Stanislav Dusko Ehrlich
Université Paris-Saclay
University College London (UCL)
O. B. Pedersen
Köpenhamns universitet
Nature Medicine
1078-8956 (ISSN) 1546170x (eISSN)
Vol. 28 2 303-314Ämneskategorier
Endokrinologi och diabetes
Annan klinisk medicin
Biomedicinsk laboratorievetenskap/teknologi
DOI
10.1038/s41591-022-01688-4
PubMed
35177860