Academic Journal
Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
| العنوان: | Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide |
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| المؤلفون: | Petros Andrikopoulos, Judith Aron-Wisnewsky, Rima Chakaroun, Antonis Myridakis, Sofia K. Forslund, Trine Nielsen, Solia Adriouch, Bridget Holmes, Julien Chilloux, Sara Vieira-Silva, Gwen Falony, Joe-Elie Salem, Fabrizio Andreelli, Eugeni Belda, Julius Kieswich, Kanta Chechi, Francesc Puig-Castellvi, Mickael Chevalier, Emmanuelle Le Chatelier, Michael T. Olanipekun, Lesley Hoyles, Renato Alves, Gerard Helft, Richard Isnard, Lars Køber, Luis Pedro Coelho, Christine Rouault, Dominique Gauguier, Jens Peter Gøtze, Edi Prifti, Philippe Froguel, The MetaCardis Consortium, Jean-Daniel Zucker, Fredrik Bäckhed, Henrik Vestergaard, Torben Hansen, Jean-Michel Oppert, Matthias Blüher, Jens Nielsen, Jeroen Raes, Peer Bork, Muhammad M. Yaqoob, Michael Stumvoll, Oluf Pedersen, S. Dusko Ehrlich, Karine Clément, Marc-Emmanuel Dumas |
| المصدر: | Nature Communications, Vol 14, Iss 1, Pp 1-18 (2023) |
| بيانات النشر: | Nature Portfolio, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Science |
| مصطلحات موضوعية: | Science |
| الوصف: | Abstract The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2041-1723 48944513 |
| Relation: | https://doaj.org/toc/2041-1723 |
| DOI: | 10.1038/s41467-023-39824-4 |
| URL الوصول: | https://doaj.org/article/12ff1d1de8474b4894451345fa26b4ed |
| رقم الانضمام: | edsdoj.12ff1d1de8474b4894451345fa26b4ed |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20411723 48944513 |
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| DOI: | 10.1038/s41467-023-39824-4 |