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Microbiome and metabolome features of the cardiometabolic disease spectrum

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Item Type:Article
Title:Microbiome and metabolome features of the cardiometabolic disease spectrum
Creators Name:Fromentin, S. and Forslund, S.K. and Chechi, K. and Aron-Wisnewsky, J. and Chakaroun, R. and Nielsen, T. and Tremaroli, V. and Ji, B. and Prifti, E. and Myridakis, A. and Chilloux, J. and Andrikopoulos, P. and Fan, Y. and Olanipekun, M.T. and Alves, R. and Adiouch, S. and Bar, N. and Talmor-Barkan, Y. and Belda, E. and Caesar, R. and Coelho, L.P. and Falony, G. and Fellahi, S. and Galan, P. and Galleron, N. and Helft, G. and Hoyles, L. and Isnard, R. and Le Chatelier, E. and Julienne, H. and Olsson, L. and Pedersen, H.K. and Pons, N. and Quinquis, B. and Rouault, C. and Roume, H. and Salem, J.E. and Schmidt, T.S.B. and Vieira-Silva, S. and Li, P. and Zimmermann-Kogadeeva, M. and Lewinter, C. and Søndertoft, N.B. and Hansen, T.H. and Gauguier, D. and Gøtze, J.P. and Køber, L. and Kornowski, R. and Vestergaard, H. and Hansen, T. and Zucker, J.D. and Hercberg, S. and Letunic, I. and Bäckhed, F. and Oppert, J.M. and Nielsen, J. and Raes, J. and Bork, P. and Stumvoll, M. and Segal, E. and Clément, K. and Dumas, M.E. and Ehrlich, S.D. and Pedersen, O.
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.
Keywords:Cardiovascular Diseases, Type 2 Diabetes Mellitus, Longitudinal Studies, Metabolome, Microbiota
Source:Nature Medicine
ISSN:1078-8956
Publisher:Nature Publishing Group
Volume:28
Number:2
Page Range:303-314
Date:17 February 2022
Official Publication:https://doi.org/10.1038/s41591-022-01688-4
PubMed:View item in PubMed

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