Microbiome and metabolome features of the cardiometabolic disease spectrum

Fromentin, S, Forslund, S, Chechi, K, Aron-Wisnewsky, J, Chakaroun, R, Nielsen, T, Tremaroli, V, Ji, B, Prifti, E, Myridakis, A, Chilloux, J, Andrikopoulos, P, Olanipekun, M, Alves, R, Adiouch, S, Bar, N, Talmor-Barkan, Y, Belda, E, Fan, Y, Caesar, R, Pedro Coelho, L, Falony, G, Fellahi, S, Galan, P, Galleron, N, Helft, G, Hoyles, L ORCID: https://orcid.org/0000-0002-6418-342X, Isnard, R, Le Chatelier, E, Julienne, H, Olsson, L, Pedersen, H, Pons, N, Quinquis, B, Rouault, C, Roume, H, Salem, J-E, Schmidt, T, Li, P, Zimmermann-Kogadeeva, M, Lewinter, C, Nadja Sondertoft, M, Hansen, T, Gauguier, D, Gøtze, J, Køber, L, Kornowski, R, Vestergaard, H, Hansen, T, Zucker, J-D, Hercber, S, Letunic, I, Bäckhed, F, Oppert, J-M, Nielsen, J, Raes, J, Bork, P, Stumvoll, M, Segal, E, Dumas, M-E, Clément, K, Ehrlich, S, Vieira-Silva, S and Metacardis Consortium, 2022. Microbiome and metabolome features of the cardiometabolic disease spectrum. Nature Medicine. ISSN 1078-8956

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Abstract

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-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 IHD cases 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 IHD cases 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 may 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 IHD cases from healthy individuals or metabolically-matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.

Item Type:	Journal article
Publication Title:	Nature Medicine
Creators:	Fromentin, S., Forslund, S., Chechi, K., Aron-Wisnewsky, J., Chakaroun, R., Nielsen, T., Tremaroli, V., Ji, B., Prifti, E., Myridakis, A., Chilloux, J., Andrikopoulos, P., Olanipekun, M., Alves, R., Adiouch, S., Bar, N., Talmor-Barkan, Y., Belda, E., Fan, Y., Caesar, R., Pedro Coelho, L., Falony, G., Fellahi, S., Galan, P., Galleron, N., Helft, G., Hoyles, L., Isnard, R., Le Chatelier, E., Julienne, H., Olsson, L., Pedersen, H., Pons, N., Quinquis, B., Rouault, C., Roume, H., Salem, J.-E., Schmidt, T., Li, P., Zimmermann-Kogadeeva, M., Lewinter, C., Nadja Sondertoft, M., Hansen, T., Gauguier, D., Gøtze, J., Køber, L., Kornowski, R., Vestergaard, H., Hansen, T., Zucker, J.-D., Hercber, S., Letunic, I., Bäckhed, F., Oppert, J.-M., Nielsen, J., Raes, J., Bork, P., Stumvoll, M., Segal, E., Dumas, M.-E., Clément, K., Ehrlich, S., Vieira-Silva, S. and Metacardis Consortium
Publisher:	Nature Research
Date:	17 February 2022
ISSN:	1078-8956
Identifiers:	Number Type 10.1038/s41591-022-01688-4 DOI 1507283 Other
Rights:	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/.
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	11 Jan 2022 16:14
Last Modified:	21 Feb 2022 09:33
URI:	https://irep.ntu.ac.uk/id/eprint/45252

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