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

Max Delbrueck Centrum Fuer Molekulare Medizin

Charité Universitätsmedizin Berlin

Deutsches Zentrum für Herz-Kreislauf-Forschung e. V.

European Molecular Biology Laboratory

Kanta Chechi

Department of Metabolism

National Heart and Lung Institute

St Mary's Hospital

Judith Aron-Wisnewsky

Université Pierre et Marie Curie (UPMC)

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

UMMISCO

Université Pierre et Marie Curie (UPMC)

Antonis Myridakis

Department of Metabolism

J. Chilloux

Department of Metabolism

Petros Andrikopoulos

Department of Metabolism

National Heart and Lung Institute

Yong Fan

Köpenhamns universitet

Michael Olanipekun

Department of Metabolism

National Heart and Lung Institute

Renato Alves

European Molecular Biology Laboratory

Solia Adiouch

Université Pierre et Marie Curie (UPMC)

Noam Bar

Weizmann Institute of Science

Yeela Talmor-Barkan

Weizmann Institute of Science

Sackler Faculty of Medicine

Rabin Medical Center Israel

Eugeni Belda

Université Pierre et Marie Curie (UPMC)

Assistance publique – Hôpitaux de Paris (AP-HP)

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

Nottingham Trent University

Department of Metabolism

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

Université Pierre et Marie Curie (UPMC)

Hugo Roume

Université Paris-Saclay

Joe-Elie Salem

Université Pierre et Marie Curie (UPMC)

Thomas S. B. Schmidt

European Molecular Biology Laboratory

Sara Vieira-Silva

Flanders Interuniversity Institute for Biotechnology

KU Leuven

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

Köpenhamns universitet

Bornholms Hospital

Torben Hansen

Köpenhamns universitet

Jean-Daniel Zucker

Université Pierre et Marie Curie (UPMC)

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

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

Assistance publique – Hôpitaux de Paris (AP-HP)

Université Pierre et Marie Curie (UPMC)

Marc-Emmanuel Dumas

National Heart and Lung Institute

Department of Metabolism

CHU Lille

Stanislav Dusko Ehrlich

University College London (UCL)

Université Paris-Saclay

O. B. Pedersen

Köpenhamns universitet

Nature Medicine

1078-8956 (ISSN)

Vol. 28 2 303-314

Ämneskategorier

Endokrinologi och diabetes

Annan klinisk medicin

Biomedicinsk laboratorievetenskap/teknologi

DOI

10.1038/s41591-022-01688-4

PubMed

35177860

Mer information

Senast uppdaterat

2022-03-03