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: 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 (Forthcoming)

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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: 7 January 2022
ISSN: 1078-8956
Identifiers:
NumberType
1507283Other
Divisions: Schools > School of Science and Technology
Record created by: Jonathan Gallacher
Date Added: 11 Jan 2022 16:14
Last Modified: 11 Jan 2022 16:14
URI: http://irep.ntu.ac.uk/id/eprint/45252

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