Microbiome and metabolome features of the cardiometabolic disease spectrum

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Title: Microbiome and metabolome features of the cardiometabolic disease spectrum
Authors: Fromentin, S
Forslund, SK
Chechi, K
Aron-Wisnewsky, J
Chakaroun, R
Nielsen, T
Tremaroli, V
Ji, B
Prifti, E
Myridakis, A
Chilloux, J
Andrikopoulos, P
Fan, Y
Olanipekun, MT
Alves, R
Adiouch, S
Bar, N
Talmor-Barkan, Y
Belda, E
Caesar, R
Coelho, LP
Falony, G
Fellahi, S
Galan, P
Galleron, N
Helft, G
Hoyles, L
Isnard, R
Le Chatelier, E
Julienne, H
Olsson, L
Pedersen, HK
Pons, N
Quinquis, B
Rouault, C
Roume, H
Salem, J-E
Schmidt, TSB
Vieira-Silva, S
Li, P
Zimmermann-Kogadeeva, M
Lewinter, C
Sondertoft, NB
Hansen, TH
Gauguier, D
Gotze, JP
Kober, L
Kornowski, R
Vestergaard, H
Hansen, T
Zucker, J-D
Hercberg, S
Letunic, I
Backhed, F
Oppert, J-M
Nielsen, J
Raes, J
Bork, P
Stumvoll, M
Segal, E
Clement, K
Dumas, M-E
Ehrlich, SD
Pedersen, O
Item Type: Journal Article
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.
Issue Date: 17-Feb-2022
Date of Acceptance: 7-Jan-2022
URI: http://hdl.handle.net/10044/1/96664
DOI: 10.1038/s41591-022-01688-4
ISSN: 1078-8956
Publisher: Nature Research
Start Page: 303
End Page: +
Journal / Book Title: Nature Medicine
Volume: 28
Issue: 2
Copyright Statement: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. © The Author(s) 2022
Sponsor/Funder: Commission of the European Communities
Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: 305312
204834/Z/16/Z
RDF01
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
CORONARY-ARTERY-DISEASE
GUT MICROBIOTA
P-CRESOL
HEART
RISK
IMPACT
SERUM
SIGNATURES
PLASMA
HEALTH
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Humans
Longitudinal Studies
Metabolome
Microbiota
Middle Aged
Humans
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Longitudinal Studies
Middle Aged
Metabolome
Microbiota
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
CORONARY-ARTERY-DISEASE
GUT MICROBIOTA
P-CRESOL
HEART
RISK
IMPACT
SERUM
SIGNATURES
PLASMA
HEALTH
11 Medical and Health Sciences
Immunology
Publication Status: Published
Online Publication Date: 2022-02-17
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
National Heart and Lung Institute



This item is licensed under a Creative Commons License Creative Commons