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Journal Articles Nature Medicine Year : 2022

Microbiome and metabolome features of the cardiometabolic disease spectrum

Kanta Chechi
  • Function : Author
Trine Nielsen
Antonis Myridakis
Julien Chilloux
Yong Fan
Renato Alves
Solia Adiouch
  • Function : Author
Noam Bar
  • Function : Author
Yeela Talmor-Barkan
  • Function : Author
Luis Pedro Coelho
  • Function : Author
Gwen Falony
  • Function : Author
Soraya Fellahi
Pilar Galan
Nathalie Galleron
  • Function : Author
Gerard Helft
  • Function : Author
Lesley Hoyles
Richard Isnard
Emmanuelle Le Chatelier
Lisa Olsson
Helle Krogh Pedersen
  • Function : Author
Nicolas Pons
  • Function : Author
Benoit Quinquis
  • Function : Author
Christine Rouault
  • Function : Author
Hugo Roume
  • Function : Author
Joe-Elie Salem
Thomas Schmidt
Sara Vieira-Silva
Peishun Li
Maria Zimmermann-Kogadeeva
Christian Lewinter
  • Function : Author
Nadja Søndertoft
Tue Hansen
Dominique Gauguier
  • Function : Author
Jens Peter Gøtze
  • Function : Author
Lars Køber
Ran Kornowski
  • Function : Author
Henrik Vestergaard
Torben Hansen
Jean-Daniel Zucker
  • Function : Author
Serge Hercberg
Ivica Letunic
  • Function : Author
Fredrik Bäckhed
  • Function : Author
Jean-Michel Oppert
Jens Nielsen
Jeroen Raes
  • Function : Author
Peer Bork
  • Function : Author
Michael Stumvoll
  • Function : Author
Eran Segal
Karine Clément
S. Dusko Ehrlich
Oluf Pedersen

Abstract

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.
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pasteur-03692581 , version 1 (09-06-2022)

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Sebastien Fromentin, Sofia Forslund, Kanta Chechi, Judith Aron-Wisnewsky, Rima Chakaroun, et al.. Microbiome and metabolome features of the cardiometabolic disease spectrum. Nature Medicine, 2022, 28 (2), pp.303-314. ⟨10.1038/s41591-022-01688-4⟩. ⟨pasteur-03692581⟩
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