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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide. / Andrikopoulos, Petros; Aron-Wisnewsky, Judith; Chakaroun, Rima; Myridakis, Antonis; Forslund, Sofia K.; Nielsen, Trine; Adriouch, Solia; Holmes, Bridget; Chilloux, Julien; Vieira-Silva, Sara; Falony, Gwen; Salem, Joe Elie; Andreelli, Fabrizio; Belda, Eugeni; Kieswich, Julius; Chechi, Kanta; Puig-Castellvi, Francesc; Chevalier, Mickael; Le Chatelier, Emmanuelle; Olanipekun, Michael T.; Hoyles, Lesley; Alves, Renato; Helft, Gerard; Isnard, Richard; Køber, Lars; Coelho, Luis Pedro; Rouault, Christine; Gauguier, Dominique; Gøtze, Jens Peter; Prifti, Edi; Froguel, Philippe; Alili, Rohia; Galijatovic, Ehm Astrid Andersson; Barthelemy, Olivier; Bastard, Jean Philippe; Batisse, Jean Paul; Bel-Lassen, Pierre; Berland, Magalie; Bittar, Randa; Blottière, Hervé; Bosquet, Frederic; Boubrit, Rachid; Bourron, Olivier; Camus, Mickael; Ciangura, Cecile; Collet, Jean Philippe; Dietrich, Arne; Djebbar, Morad; Doré, Angélique; Engelbrechtsen, Line; Fezeu, Leopold; Fromentin, Sebastien; Pons, Nicolas; Graine, Marianne; Grünemann, Caroline; Hartemann, Agnes; Hartmann, Bolette; Hornbak, Malene; Jaqueminet, Sophie; Jørgensen, Niklas Rye; Julienne, Hanna; Justesen, Johanne; Kammer, Judith; Karup, Nikolaj; Kozlowski, Ruby; Kuhn, Michael; Lejard, Véronique; Letunic, Ivica; Levenez, Florence; Marko, Lajos; Martinez-Gili, Laura; Massey, Robin; Maziers, Nicolas; Moitinho-Silva, Lucas; Montalescot, Gilles; Neves, Ana Luisa; Le Pavin, Laetitia Pasero; Pousset, Francoise; Rodriguez-Martinez, Andrea; Schmidt, Sebastien; Schütz, Tatjana; Silva, Lucas; Silvain, Johanne; Svendstrup, Mathilde; Swartz, Timothy D.; Vanduyvenboden, Thierry; Verger, Eric O.; Walther, Stefanie; Zucker, Jean Daniel; Bäckhed, Fredrik; Vestergaard, Henrik; Hansen, Torben; Oppert, Jean Michel; Blüher, Matthias; Nielsen, Jens; Raes, Jeroen; Bork, Peer; Yaqoob, Muhammad M.; Stumvoll, Michael; Pedersen, Oluf; Ehrlich, S. Dusko; Clément, Karine; Dumas, Marc Emmanuel.
In:
Nature Communications, Vol. 14, 5843, 2023.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Andrikopoulos, P, Aron-Wisnewsky, J, Chakaroun, R, Myridakis, A, Forslund, SK, Nielsen, T, Adriouch, S, Holmes, B, Chilloux, J, Vieira-Silva, S, Falony, G, Salem, JE, Andreelli, F, Belda, E, Kieswich, J, Chechi, K, Puig-Castellvi, F, Chevalier, M, Le Chatelier, E, Olanipekun, MT, Hoyles, L, Alves, R, Helft, G, Isnard, R
, Køber, L, Coelho, LP, Rouault, C, Gauguier, D
, Gøtze, JP, Prifti, E, Froguel, P, Alili, R, Galijatovic, EAA, Barthelemy, O, Bastard, JP, Batisse, JP, Bel-Lassen, P, Berland, M, Bittar, R, Blottière, H, Bosquet, F, Boubrit, R, Bourron, O, Camus, M, Ciangura, C, Collet, JP, Dietrich, A, Djebbar, M, Doré, A
, Engelbrechtsen, L, Fezeu, L, Fromentin, S, Pons, N, Graine, M, Grünemann, C, Hartemann, A
, Hartmann, B, Hornbak, M, Jaqueminet, S
, Jørgensen, NR, Julienne, H
, Justesen, J, Kammer, J, Karup, N, Kozlowski, R, Kuhn, M, Lejard, V, Letunic, I, Levenez, F, Marko, L, Martinez-Gili, L, Massey, R, Maziers, N, Moitinho-Silva, L, Montalescot, G, Neves, AL, Le Pavin, LP, Pousset, F, Rodriguez-Martinez, A, Schmidt, S, Schütz, T, Silva, L, Silvain, J, Svendstrup, M, Swartz, TD, Vanduyvenboden, T, Verger, EO, Walther, S, Zucker, JD, Bäckhed, F
, Vestergaard, H, Hansen, T, Oppert, JM, Blüher, M, Nielsen, J, Raes, J, Bork, P, Yaqoob, MM, Stumvoll, M
, Pedersen, O, Ehrlich, SD, Clément, K & Dumas, ME 2023, '
Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide',
Nature Communications, vol. 14, 5843.
https://doi.org/10.1038/s41467-023-39824-4APA
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., ... Dumas, M. E. (2023).
Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide.
Nature Communications,
14, [5843].
https://doi.org/10.1038/s41467-023-39824-4Vancouver
Andrikopoulos P, Aron-Wisnewsky J, Chakaroun R, Myridakis A, Forslund SK, Nielsen T et al.
Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide.
Nature Communications. 2023;14. 5843.
https://doi.org/10.1038/s41467-023-39824-4Author
Andrikopoulos, Petros ; Aron-Wisnewsky, Judith ; Chakaroun, Rima ; Myridakis, Antonis ; Forslund, Sofia K. ; Nielsen, Trine ; Adriouch, Solia ; Holmes, Bridget ; Chilloux, Julien ; Vieira-Silva, Sara ; Falony, Gwen ; Salem, Joe Elie ; Andreelli, Fabrizio ; Belda, Eugeni ; Kieswich, Julius ; Chechi, Kanta ; Puig-Castellvi, Francesc ; Chevalier, Mickael ; Le Chatelier, Emmanuelle ; Olanipekun, Michael T. ; Hoyles, Lesley ; Alves, Renato ; Helft, Gerard ; Isnard, Richard ; Køber, Lars ; Coelho, Luis Pedro ; Rouault, Christine ; Gauguier, Dominique ; Gøtze, Jens Peter ; Prifti, Edi ; Froguel, Philippe ; Alili, Rohia ; Galijatovic, Ehm Astrid Andersson ; Barthelemy, Olivier ; Bastard, Jean Philippe ; Batisse, Jean Paul ; Bel-Lassen, Pierre ; Berland, Magalie ; Bittar, Randa ; Blottière, Hervé ; Bosquet, Frederic ; Boubrit, Rachid ; Bourron, Olivier ; Camus, Mickael ; Ciangura, Cecile ; Collet, Jean Philippe ; Dietrich, Arne ; Djebbar, Morad ; Doré, Angélique ; Engelbrechtsen, Line ; Fezeu, Leopold ; Fromentin, Sebastien ; Pons, Nicolas ; Graine, Marianne ; Grünemann, Caroline ; Hartemann, Agnes ; Hartmann, Bolette ; Hornbak, Malene ; Jaqueminet, Sophie ; Jørgensen, Niklas Rye ; Julienne, Hanna ; Justesen, Johanne ; Kammer, Judith ; Karup, Nikolaj ; Kozlowski, Ruby ; Kuhn, Michael ; Lejard, Véronique ; Letunic, Ivica ; Levenez, Florence ; Marko, Lajos ; Martinez-Gili, Laura ; Massey, Robin ; Maziers, Nicolas ; Moitinho-Silva, Lucas ; Montalescot, Gilles ; Neves, Ana Luisa ; Le Pavin, Laetitia Pasero ; Pousset, Francoise ; Rodriguez-Martinez, Andrea ; Schmidt, Sebastien ; Schütz, Tatjana ; Silva, Lucas ; Silvain, Johanne ; Svendstrup, Mathilde ; Swartz, Timothy D. ; Vanduyvenboden, Thierry ; Verger, Eric O. ; Walther, Stefanie ; Zucker, Jean Daniel ; Bäckhed, Fredrik ; Vestergaard, Henrik ; Hansen, Torben ; Oppert, Jean Michel ; Blüher, Matthias ; Nielsen, Jens ; Raes, Jeroen ; Bork, Peer ; Yaqoob, Muhammad M. ; Stumvoll, Michael ; Pedersen, Oluf ; Ehrlich, S. Dusko ; Clément, Karine ; Dumas, Marc Emmanuel. / Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide. In: Nature Communications. 2023 ; Vol. 14.
Bibtex
@article{0cb3ef1b53f34280b1f25552025d2b73,
title = "Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide",
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.",
author = "Petros Andrikopoulos and Judith Aron-Wisnewsky and Rima Chakaroun and Antonis Myridakis and Forslund, {Sofia K.} and Trine Nielsen and Solia Adriouch and Bridget Holmes and Julien Chilloux and Sara Vieira-Silva and Gwen Falony and Salem, {Joe Elie} and Fabrizio Andreelli and Eugeni Belda and Julius Kieswich and Kanta Chechi and Francesc Puig-Castellvi and Mickael Chevalier and {Le Chatelier}, Emmanuelle and Olanipekun, {Michael T.} and Lesley Hoyles and Renato Alves and Gerard Helft and Richard Isnard and Lars K{\o}ber and Coelho, {Luis Pedro} and Christine Rouault and Dominique Gauguier and G{\o}tze, {Jens Peter} and Edi Prifti and Philippe Froguel and Rohia Alili and Galijatovic, {Ehm Astrid Andersson} and Olivier Barthelemy and Bastard, {Jean Philippe} and Batisse, {Jean Paul} and Pierre Bel-Lassen and Magalie Berland and Randa Bittar and Herv{\'e} Blotti{\`e}re and Frederic Bosquet and Rachid Boubrit and Olivier Bourron and Mickael Camus and Cecile Ciangura and Collet, {Jean Philippe} and Arne Dietrich and Morad Djebbar and Ang{\'e}lique Dor{\'e} and Line Engelbrechtsen and Leopold Fezeu and Sebastien Fromentin and Nicolas Pons and Marianne Graine and Caroline Gr{\"u}nemann and Agnes Hartemann and Bolette Hartmann and Malene Hornbak and Sophie Jaqueminet and J{\o}rgensen, {Niklas Rye} and Hanna Julienne and Johanne Justesen and Judith Kammer and Nikolaj Karup and Ruby Kozlowski and Michael Kuhn and V{\'e}ronique Lejard and Ivica Letunic and Florence Levenez and Lajos Marko and Laura Martinez-Gili and Robin Massey and Nicolas Maziers and Lucas Moitinho-Silva and Gilles Montalescot and Neves, {Ana Luisa} and {Le Pavin}, {Laetitia Pasero} and Francoise Pousset and Andrea Rodriguez-Martinez and Sebastien Schmidt and Tatjana Sch{\"u}tz and Lucas Silva and Johanne Silvain and Mathilde Svendstrup and Swartz, {Timothy D.} and Thierry Vanduyvenboden and Verger, {Eric O.} and Stefanie Walther and Zucker, {Jean Daniel} and Fredrik B{\"a}ckhed and Henrik Vestergaard and Torben Hansen and Oppert, {Jean Michel} and Matthias Bl{\"u}her and Jens Nielsen and Jeroen Raes and Peer Bork and Yaqoob, {Muhammad M.} and Michael Stumvoll and Oluf Pedersen and Ehrlich, {S. Dusko} and Karine Cl{\'e}ment and Dumas, {Marc Emmanuel}",
note = "Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",
year = "2023",
doi = "10.1038/s41467-023-39824-4",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
}
RIS
TY - JOUR
T1 - Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
AU - Andrikopoulos, Petros
AU - Aron-Wisnewsky, Judith
AU - Chakaroun, Rima
AU - Myridakis, Antonis
AU - Forslund, Sofia K.
AU - Nielsen, Trine
AU - Adriouch, Solia
AU - Holmes, Bridget
AU - Chilloux, Julien
AU - Vieira-Silva, Sara
AU - Falony, Gwen
AU - Salem, Joe Elie
AU - Andreelli, Fabrizio
AU - Belda, Eugeni
AU - Kieswich, Julius
AU - Chechi, Kanta
AU - Puig-Castellvi, Francesc
AU - Chevalier, Mickael
AU - Le Chatelier, Emmanuelle
AU - Olanipekun, Michael T.
AU - Hoyles, Lesley
AU - Alves, Renato
AU - Helft, Gerard
AU - Isnard, Richard
AU - Køber, Lars
AU - Coelho, Luis Pedro
AU - Rouault, Christine
AU - Gauguier, Dominique
AU - Gøtze, Jens Peter
AU - Prifti, Edi
AU - Froguel, Philippe
AU - Alili, Rohia
AU - Galijatovic, Ehm Astrid Andersson
AU - Barthelemy, Olivier
AU - Bastard, Jean Philippe
AU - Batisse, Jean Paul
AU - Bel-Lassen, Pierre
AU - Berland, Magalie
AU - Bittar, Randa
AU - Blottière, Hervé
AU - Bosquet, Frederic
AU - Boubrit, Rachid
AU - Bourron, Olivier
AU - Camus, Mickael
AU - Ciangura, Cecile
AU - Collet, Jean Philippe
AU - Dietrich, Arne
AU - Djebbar, Morad
AU - Doré, Angélique
AU - Engelbrechtsen, Line
AU - Fezeu, Leopold
AU - Fromentin, Sebastien
AU - Pons, Nicolas
AU - Graine, Marianne
AU - Grünemann, Caroline
AU - Hartemann, Agnes
AU - Hartmann, Bolette
AU - Hornbak, Malene
AU - Jaqueminet, Sophie
AU - Jørgensen, Niklas Rye
AU - Julienne, Hanna
AU - Justesen, Johanne
AU - Kammer, Judith
AU - Karup, Nikolaj
AU - Kozlowski, Ruby
AU - Kuhn, Michael
AU - Lejard, Véronique
AU - Letunic, Ivica
AU - Levenez, Florence
AU - Marko, Lajos
AU - Martinez-Gili, Laura
AU - Massey, Robin
AU - Maziers, Nicolas
AU - Moitinho-Silva, Lucas
AU - Montalescot, Gilles
AU - Neves, Ana Luisa
AU - Le Pavin, Laetitia Pasero
AU - Pousset, Francoise
AU - Rodriguez-Martinez, Andrea
AU - Schmidt, Sebastien
AU - Schütz, Tatjana
AU - Silva, Lucas
AU - Silvain, Johanne
AU - Svendstrup, Mathilde
AU - Swartz, Timothy D.
AU - Vanduyvenboden, Thierry
AU - Verger, Eric O.
AU - Walther, Stefanie
AU - Zucker, Jean Daniel
AU - Bäckhed, Fredrik
AU - Vestergaard, Henrik
AU - Hansen, Torben
AU - Oppert, Jean Michel
AU - Blüher, Matthias
AU - Nielsen, Jens
AU - Raes, Jeroen
AU - Bork, Peer
AU - Yaqoob, Muhammad M.
AU - Stumvoll, Michael
AU - Pedersen, Oluf
AU - Ehrlich, S. Dusko
AU - Clément, Karine
AU - Dumas, Marc Emmanuel
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-023-39824-4
DO - 10.1038/s41467-023-39824-4
M3 - Journal article
C2 - 37730687
AN - SCOPUS:85171810387
VL - 14
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 5843
ER -
