Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
| Title: | Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide |
|---|---|
| Authors: | Andrikopoulos, P.; Aron-Wisnewsky, J.; Chakaroun, R.; Myridakis, A.; Forslund, S.K.; Nielsen, T.; Adriouch, S.; Holmes, B.; Chilloux, J.; Vieira-Silva, S.; Falony, G.; Salem, J.E.; Andreelli, F.; Belda, E.; Kieswich, J.; Chechi, K.; Puig-Castellvi, F.; Chevalier, M.; Le Chatelier, E.; Olanipekun, M.T.; Hoyles, L.; Alves, R.; Helft, G.; Isnard, R.; Køber, L.; Coelho, L.P.; Rouault, C.; Gauguier, D.; Gøtze, J.P.; Prifti, E.; Froguel, P.; Zucker, J.D.; Bäckhed, F.; Vestergaard, H.; Hansen, T.; Oppert, J.M.; Blüher, M.; Nielsen, J.; Raes, J.; Bork, P.; Yaqoob, M.M.; Stumvoll, M.; Pedersen, O.; Ehrlich, S.D.; Clément, K.; Dumas, M.E. |
| Publisher Information: | Nature Publishing Group |
| Publication Year: | 2023 |
| Collection: | Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| Subject Terms: | Cardiovascular and Metabolic Diseases; Topic 2: Molecular Processes and Therapies; Topic 3: Integrative Biomedicine |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf; other |
| Language: | English |
| Relation: | https://edoc.mdc-berlin.de/id/eprint/23742/1/23742oa.pdf; https://edoc.mdc-berlin.de/id/eprint/23742/2/23742suppl.zip; Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide. Andrikopoulos, P., Aron-Wisnewsky, J., Chakaroun, R., Myridakis, A., Forslund, S.K., Nielsen, T., Adriouch, S., Holmes, B., Chilloux, J., Vieira-Silva, S., Falony, G., Salem, J.E., Andreelli, F., Belda, E., Kieswich, J., Chechi, K., Puig-Castellvi, F., Chevalier, M., Le Chatelier, E., Olanipekun, M.T., Hoyles, L., Alves, R., Helft, G., Isnard, R., Køber, L., Coelho, L.P., Rouault, C., Gauguier, D., Gøtze, J.P., Prifti, E., Froguel, P., Zucker, J.D., Bäckhed, F., Vestergaard, H., Hansen, T., Oppert, J.M., Blüher, M., Nielsen, J., Raes, J., Bork, P., Yaqoob, M.M., Stumvoll, M., Pedersen, O., Ehrlich, S.D., Clément, K. and Dumas, M.E. Nature Communications 14 (1): 5843. 20 September 2023; PMID:37730687; https://doi.org/10.1038/s41467-023-39824-4 |
| DOI: | 10.1038/s41467-023-39824-4 |
| Availability: | https://edoc.mdc-berlin.de/id/eprint/23742/; https://edoc.mdc-berlin.de/23742/; https://doi.org/10.1038/s41467-023-39824-4 |
| Rights: | cc_by_4 ; cc_by_nd_4 |
| Accession Number: | edsbas.8379FE45 |
| Database: | BASE |