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
Deutsches Zentrum für Herz-Kreislauf-Forshung (DZHK)
European Molecular Biology Laboratory
Max Delbrueck Centrum Fuer Molekulare Medizin
Charité Universitätsmedizin Berlin
Kanta Chechi
Imperial College London
National Heart and Lung Institute
St Mary's Hospital
Judith Aron-Wisnewsky
Assistance publique – Hôpitaux de Paris (AP-HP)
Sorbonne Université
Rima Chakaroun
Universität Leipzig
Trine Nielsen
Köpenhamns universitet
Valentina Tremaroli
Wallenberg Lab.
Boyang Ji
Chalmers, Biologi och bioteknik, Systembiologi
Edi Prifti
UMMISCO
Sorbonne Université
Antonis Myridakis
Imperial College London
J. Chilloux
Imperial College London
Petros Andrikopoulos
National Heart and Lung Institute
Imperial College London
Yong Fan
Köpenhamns universitet
Michael Olanipekun
National Heart and Lung Institute
Imperial College London
Renato Alves
European Molecular Biology Laboratory
Solia Adiouch
Sorbonne Université
Noam Bar
Weizmann Institute of Science
Yeela Talmor-Barkan
Weizmann Institute of Science
Rabin Medical Center
Tel Aviv University
Eugeni Belda
Assistance publique – Hôpitaux de Paris (AP-HP)
Integrative Phenomics
Sorbonne Université
Robert Caesar
Wallenberg Lab.
Luis P. Coelho
European Molecular Biology Laboratory
Gwen Falony
KU Leuven
Flanders Interuniversity Institute for Biotechnology
Soraya Fellahi
Henri-Mondor University Hospital
Pilar Galan
Université Paris-Saclay
Nathalie Galleron
Université Paris-Saclay
Gerard Helft
Assistance publique – Hôpitaux de Paris (AP-HP)
L. Hoyles
Nottingham Trent University
Imperial College London
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
H. Vestergaard
Bornholms Hospital
Köpenhamns universitet
Torben Hansen
Köpenhamns universitet
Jean-Daniel Zucker
Sorbonne Université
UMMISCO
Serge Hercberg
Université Paris Nord
Ivica Letunic
Biobyte Solutions
Fredrik Bäckhed
Wallenberg Lab.
Köpenhamns universitet
Jean-Michel Oppert
Assistance publique – Hôpitaux de Paris (AP-HP)
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
Jeroen Raes
KU Leuven
Flanders Interuniversity Institute for Biotechnology
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
Lille University Hospital
Imperial College London
National Heart and Lung Institute
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 (SSIF 2011)
Endokrinologi och diabetes
Annan klinisk medicin
Biomedicinsk laboratorievetenskap/teknologi
DOI
10.1038/s41591-022-01688-4
PubMed
35177860