Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

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Andrikopoulos, PetrosImperial College of Science, Technology and Medicine (author)

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

Article/chapterEnglish2023

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2023
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LIBRIS-ID:oai:research.chalmers.se:fd008736-15a5-4c2b-bfd9-429ad93330a8
https://research.chalmers.se/publication/537644URI
https://doi.org/10.1038/s41467-023-39824-4DOI
https://gup.ub.gu.se/publication/330408URI

Supplementary language notes

Language:English
Summary in:English

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SwePubSwePub

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Urologi och njurmedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Urology and Nephrology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
l-carnitine
molecular-mechanisms
microbial-metabolism
risk
disease
consumption
marker
phosphatidylcholine
atherosclerosis
angiogenesis
Science & Technology - Other Topics

Added entries (persons, corporate bodies, meetings, titles ...)

Aron-Wisnewsky, JudithAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Chakaroun, Rima,1983Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xchrim (author)
Myridakis, AntonisImperial College of Science, Technology and Medicine (author)
Forslund, Sofia K.Charité Universitätsmedizin Berlin,Charité University Medicine Berlin,Max Delbrueck Centrum Fuer Molekulare Medizin,The Max Delbrück Center for Molecular Medicine,European Molecular Biology Laboratory (author)
Nielsen, TrineNovo Nordisk Fonden,Novo Nordisk Foundation (author)
Adriouch, Solia (author)
Holmes, BridgetDanone Research (author)
Chilloux, J.Imperial College of Science, Technology and Medicine (author)
Vieira-Silva, SaraKatholieke Universiteit Leuven,Flanders Interuniversity Institute for Biotechnology,Johannes Gutenberg-Universität Mainz,Johannes Gutenberg University Mainz (author)
Falony, GwenFlanders Interuniversity Institute for Biotechnology,Katholieke Universiteit Leuven,Johannes Gutenberg-Universität Mainz,Johannes Gutenberg University Mainz (author)
Salem, Joe-ElieAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Andreelli, FabrizioAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Belda, Eugeni (author)
Kieswich, Julius (author)
Chechi, KantaImperial College of Science, Technology and Medicine (author)
Puig-Castellvi, Francesc (author)
Chevalier, Mickael (author)
Le Chatelier, EmmanuelleUniversité Paris-Saclay,University Paris-Saclay (author)
Olanipekun, MichaelImperial College of Science, Technology and Medicine (author)
Hoyles, L.Nottingham Trent University (author)
Alves, RenatoEuropean Molecular Biology Laboratory (author)
Helft, GerardAssistance publique – Hôpitaux de Paris (AP-HP),Inserm Transfert SA (author)
Isnard, RichardAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Køber, LarsRigshospitalet (author)
Coelho, Luis P.European Molecular Biology Laboratory (author)
Rouault, Christine (author)
Gauguier, DominiqueMcGill University (author)
Gøtze, Jens P.Rigshospitalet (author)
Prifti, Edi (author)
Froguel, PhilippeImperial College of Science, Technology and Medicine (author)
Alili, Rohia (author)
Galijatovic, Ehm Astrid AnderssonNovo Nordisk Fonden,Novo Nordisk Foundation (author)
Barthelemy, OlivierAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Bastard, Jean-Phillippe (author)
Batisse, Jean-PaulAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Bel-Lassen, Pierre (author)
Berland, MagalieUniversité Paris-Saclay,University Paris-Saclay (author)
Bittar, RandaAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Blottière, HervéUniversité Paris-Saclay,University Paris-Saclay (author)
Bosquet, FredericAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Boubrit, RachidAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Bourron, OlivierAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Camus, Mickael (author)
Ciangura, CecileAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Collet, Jean-PhilippeAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Dietrich, ArneUniversität Leipzig,Leipzig University (author)
Djebbar, MoradAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Doré, AngéliqueUniversité Paris-Saclay,University Paris-Saclay (author)
Engelbrechtsen, LineNovo Nordisk Fonden,Novo Nordisk Foundation (author)
Fezeu, LeopoldConservatoire National des Arts et Metiers (author)
Fromentin, SebastienUniversité Paris-Saclay,University Paris-Saclay (author)
Pons, NicolasUniversité Paris-Saclay,University Paris-Saclay (author)
Graine, Marianne (author)
Grünemann, CarolineUniversität Leipzig,Leipzig University (author)
Hartemann, AgnesAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Hartmann, BoletteNovo Nordisk Fonden,Novo Nordisk Foundation (author)
Hornbak, MaleneNovo Nordisk Fonden,Novo Nordisk Foundation (author)
Jaqueminet, SophieAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Jørgensen, Niklas RyeRigshospitalet (author)
Julienne, HannaUniversité Paris-Saclay,University Paris-Saclay (author)
Justesen, JohanneNovo Nordisk Fonden,Novo Nordisk Foundation (author)
Kammer, JudithUniversität Leipzig,Leipzig University (author)
Karup, NikolajNovo Nordisk Fonden,Novo Nordisk Foundation (author)
Kozlowski, RubyImperial College of Science, Technology and Medicine (author)
Kuhn, MichaelEuropean Molecular Biology Laboratory (author)
Lejard, VéroniqueUniversité Paris-Saclay,University Paris-Saclay (author)
Letunic, IvicaEuropean Molecular Biology Laboratory (author)
Levenez, FlorenceUniversité Paris-Saclay,University Paris-Saclay (author)
Markó, LajosMax Delbrueck Centrum Fuer Molekulare Medizin,The Max Delbrück Center for Molecular Medicine (author)
Martinez-Gili, LauraImperial College of Science, Technology and Medicine (author)
Massey, RobinUniversité Paris-Saclay,University Paris-Saclay (author)
Maziers, NicolasUniversité Paris-Saclay,University Paris-Saclay (author)
Moitinho-Silva, LucasEuropean Molecular Biology Laboratory (author)
Montalescot, GillesAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Neves, Ana LuisaImperial College of Science, Technology and Medicine (author)
Le Pavin, Laetitia PaseroUniversité Paris-Saclay,University Paris-Saclay (author)
Pousset, FrancoiseAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Rodriguez-Martinez, AndreaImperial College of Science, Technology and Medicine (author)
Schmidt, SebastianEuropean Molecular Biology Laboratory (author)
Schütz, TatjanaUniversität Leipzig,Leipzig University (author)
Silva, LucasEuropean Molecular Biology Laboratory (author)
Silvain, JohanneAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Svendstrup, MathildeNovo Nordisk Fonden,Novo Nordisk Foundation (author)
Swartz, Timothy (author)
Vanduyvenboden, ThierryUniversité Paris-Saclay,University Paris-Saclay (author)
Verger, EricUniversité de Montpellier,University of Montpellier (author)
Walther, StefanieUniversität Leipzig,Leipzig University (author)
Zucker, Jean-Daniel (author)
Bäckhed, Fredrik,1973Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xbafre (author)
Vestergaard, H.Novo Nordisk Fonden,Novo Nordisk Foundation (author)
Hansen, TorbenNovo Nordisk Fonden,Novo Nordisk Foundation (author)
Oppert, Jean-MichelAssistance publique – Hôpitaux de Paris (AP-HP) (author)
Bluher, M.Universität Leipzig,Leipzig University (author)
Nielsen, Jens B,1962Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj (author)
Raes, JeroenKatholieke Universiteit Leuven,Flanders Interuniversity Institute for Biotechnology (author)
Bork, PeerEuropean Molecular Biology Laboratory,Max Delbrueck Centrum Fuer Molekulare Medizin,The Max Delbrück Center for Molecular Medicine,Yonsei University,Julius-Maximilians Universität Würzburg,University of Würzburg (author)
Yaqoob, Muhammad Magdi (author)
Stumvoll, M.Universität Leipzig,Leipzig University (author)
Pedersen, O. B.Novo Nordisk Fonden,Novo Nordisk Foundation (author)
Clément, K. (author)
Dumas, M. E. (author)
MetaCardis, Consortium (author)
Imperial College of Science, Technology and MedicineAssistance publique – Hôpitaux de Paris (AP-HP) (creator_code:org_t)

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In:Nature Communications14:12041-17232041-1723

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By the author/editor: Andrikopoulos, P ...; Aron-Wisnewsky, ...; Chakaroun, Rima, ...; Myridakis, Anton ...; Forslund, Sofia ...; Nielsen, Trine; show more...; Adriouch, Solia; Holmes, Bridget; Chilloux, J.; Vieira-Silva, Sa ...; Falony, Gwen; Salem, Joe-Elie; Andreelli, Fabri ...; Belda, Eugeni; Kieswich, Julius; Chechi, Kanta; Puig-Castellvi, ...; Chevalier, Micka ...; Le Chatelier, Em ...; Olanipekun, Mich ...; Hoyles, L.; Alves, Renato; Helft, Gerard; Isnard, Richard; Køber, Lars; Coelho, Luis P.; Rouault, Christi ...; Gauguier, Domini ...; Gøtze, Jens P.; Prifti, Edi; Froguel, Philipp ...; Alili, Rohia; Galijatovic, Ehm ...; Barthelemy, Oliv ...; Bastard, Jean-Ph ...; Batisse, Jean-Pa ...; Bel-Lassen, Pier ...; Berland, Magalie; Bittar, Randa; Blottière, Hervé; Bosquet, Frederi ...; Boubrit, Rachid; Bourron, Olivier; Camus, Mickael; Ciangura, Cecile; Collet, Jean-Phi ...; Dietrich, Arne; Djebbar, Morad; Doré, Angélique; Engelbrechtsen, ...; Fezeu, Leopold; Fromentin, Sebas ...; Pons, Nicolas; Graine, Marianne; Grünemann, Carol ...; Hartemann, Agnes; Hartmann, Bolett ...; Hornbak, Malene; Jaqueminet, Soph ...; Jørgensen, Nikla ...; Julienne, Hanna; Justesen, Johann ...; Kammer, Judith; Karup, Nikolaj; Kozlowski, Ruby; Kuhn, Michael; Lejard, Véroniqu ...; Letunic, Ivica; Levenez, Florenc ...; Markó, Lajos; Martinez-Gili, L ...; Massey, Robin; Maziers, Nicolas; Moitinho-Silva, ...; Montalescot, Gil ...; Neves, Ana Luisa; Le Pavin, Laetit ...; Pousset, Francoi ...; Rodriguez-Martin ...; Schmidt, Sebasti ...; Schütz, Tatjana; Silva, Lucas; Silvain, Johanne; Svendstrup, Math ...; Swartz, Timothy; Vanduyvenboden, ...; Verger, Eric; Walther, Stefani ...; Zucker, Jean-Dan ...; Bäckhed, Fredrik ...; Vestergaard, H.; Hansen, Torben; Oppert, Jean-Mic ...; Bluher, M.; Nielsen, Jens B, ...; Raes, Jeroen; Bork, Peer; Yaqoob, Muhammad ...; Stumvoll, M.; Pedersen, O. B.; Clément, K.; Dumas, M. E.; MetaCardis, Cons ...; show less...

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