Microbiome and metabolome features of the cardiometabolic disease spectrum

Sebastien Fromentin, Sofia K. Forslund, Kanta Chechi, Judith Aron-Wisnewsky, Rima Chakaroun, Trine Nielsen, Valentina Tremaroli, Boyang Ji, Edi Prifti, Antonis Myridakis, Julien Chilloux, Petros Andrikopoulos, Yong Fan, Michael T. Olanipekun, Renato Alves, Solia Adiouch, Noam Bar, Yeela Talmor-Barkan, Eugeni Belda, Robert CaesarLuis Pedro Coelho, Gwen Falony, Soraya Fellahi, Pilar Galan, Nathalie Galleron, Gerard Helft, Lesley Hoyles, Richard Isnard, Emmanuelle Le Chatelier, Hanna Julienne, Lisa Olsson, Helle Krogh Pedersen, Nicolas Pons, Benoit Quinquis, Christine Rouault, Hugo Roume, Joe Elie Salem, Thomas S.B. Schmidt, Sara Vieira-Silva, Peishun Li, Maria Zimmermann-Kogadeeva, Christian Lewinter, Nadja B. Søndertoft, Tue H. Hansen, Dominique Gauguier, Jens Peter Gøtze, Lars Køber, Ran Kornowski, Henrik Vestergaard, Torben Hansen, Jean Daniel Zucker, Serge Hercberg, Ivica Letunic, Fredrik Bäckhed, Jean Michel Oppert, Jens Nielsen, Jeroen Raes, Peer Bork, Michael Stumvoll, Eran Segal, Karine Clément, Marc Emmanuel Dumas, S. Dusko Ehrlich*, Oluf Pedersen

*Corresponding author for this work
92 Citations (Scopus)


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.

Original languageEnglish
JournalNature Medicine
Issue number2
Pages (from-to)303-314
Number of pages12
Publication statusPublished - Feb 2022


  • Cardiovascular Diseases
  • Diabetes Mellitus, Type 2
  • Humans
  • Longitudinal Studies
  • Metabolome
  • Microbiota
  • Middle Aged


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