Microbiome and metabolome features of the cardiometabolic disease spectrum
Journal article, 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.
Author
Sebastien Fromentin
University Paris-Saclay
Sofia K. Forslund
Charité University Medicine Berlin
Deutsches Zentrum für Herz-Kreislauf-Forschung e. V.
The Max Delbrück Center for Molecular Medicine
European Molecular Biology Laboratory
Kanta Chechi
St Mary's Hospital
Department of Metabolism
National Heart and Lung Institute
Judith Aron-Wisnewsky
Sorbonne University
Assistance publique – Hôpitaux de Paris (AP-HP)
Rima Chakaroun
Leipzig University
Trine Nielsen
University of Copenhagen
Valentina Tremaroli
Wallenberg Lab.
Boyang Ji
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Edi Prifti
Sorbonne University
UMMISCO
Antonis Myridakis
Department of Metabolism
J. Chilloux
Department of Metabolism
Petros Andrikopoulos
Department of Metabolism
National Heart and Lung Institute
Yong Fan
University of Copenhagen
Michael Olanipekun
Department of Metabolism
National Heart and Lung Institute
Renato Alves
European Molecular Biology Laboratory
Solia Adiouch
Sorbonne University
Noam Bar
Weizmann Institute of Science
Yeela Talmor-Barkan
Tel Aviv University
Rabin Medical Center
Weizmann Institute of Science
Eugeni Belda
Integrative Phenomics
Assistance publique – Hôpitaux de Paris (AP-HP)
Sorbonne University
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
University Paris-Saclay
Nathalie Galleron
University 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
University Paris-Saclay
Hanna Julienne
University Paris-Saclay
Lisa M. Olsson
Wallenberg Lab.
Helle K. Pedersen
University of Copenhagen
Nicolas Pons
University Paris-Saclay
Benoit Quinquis
University Paris-Saclay
Christine Rouault
Sorbonne University
Hugo Roume
University Paris-Saclay
Joe-Elie Salem
Sorbonne University
Thomas S. B. Schmidt
European Molecular Biology Laboratory
Sara Vieira-Silva
Flanders Interuniversity Institute for Biotechnology
KU Leuven
Peishun Li
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Maria Zimmermann-Kogadeeva
European Molecular Biology Laboratory
Christian Lewinter
University of Copenhagen
Nadja B. Søndertoft
University of Copenhagen
Tue H. Hansen
University of Copenhagen
Dominique Gauguier
Paris Descartes University
Jens P. Gøtze
University of Copenhagen
Lars Køber
University of Copenhagen
Ran Kornowski
Rabin Medical Center
H. Vestergaard
Bornholms Hospital
University of Copenhagen
Torben Hansen
University of Copenhagen
Jean-Daniel Zucker
Sorbonne University
UMMISCO
Serge Hercberg
University of Paris North
Ivica Letunic
Biobyte Solutions
Fredrik Bäckhed
University of Copenhagen
Wallenberg Lab.
Jean-Michel Oppert
Assistance publique – Hôpitaux de Paris (AP-HP)
Jens B Nielsen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Jeroen Raes
Flanders Interuniversity Institute for Biotechnology
KU Leuven
Peer Bork
European Molecular Biology Laboratory
M. Stumvoll
Leipzig University
Eran Segal
Weizmann Institute of Science
K. Clement
Assistance publique – Hôpitaux de Paris (AP-HP)
Sorbonne University
Marc-Emmanuel Dumas
National Heart and Lung Institute
CHU Lille
Department of Metabolism
Stanislav Dusko Ehrlich
University Paris-Saclay
University College London (UCL)
O. B. Pedersen
University of Copenhagen
Nature Medicine
1078-8956 (ISSN) 1546170x (eISSN)
Vol. 28 2 303-314Subject Categories (SSIF 2011)
Endocrinology and Diabetes
Other Clinical Medicine
Biomedical Laboratory Science/Technology
DOI
10.1038/s41591-022-01688-4
PubMed
35177860