ArticleNature communications2023
Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 5 pooled it
10.2field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 5 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- STROBE-causal machine learning for the human microbiome: systematic review on methodological innovations and validation frameworks.Frontiers in microbiology · 2026Pooled it
- The Effect of Red Meat Consumption on Circulating, Urinary, and Fecal Trimethylamine-N-Oxide: A Systematic Review and Narrative Synthesis of Randomized Controlled Trials.Advances in nutrition (Bethesda, Md.) · 2025Pooled it
- The microbiome-derived metabolite trimethylamine N-oxide is associated with chronic kidney disease risk.Applied microbiology and biotechnology · 2025Pooled it
- The Association Between Lifestyle Interventions and Trimethylamine N-Oxide: A Systematic-Narrative Hybrid Literature Review.Nutrients · 2025Pooled it
- Beyond just correlation: causal machine learning for the microbiome, from prediction to health policy with econometric tools.Frontiers in microbiology · 2025Pooled it
- Modulating effects of microbiota on synbiotic intervention outcomes for microbiota-derived trimethylamine, trimethylamine N-oxide and indoxyl sulfate in healthy young medical students: insights from a 12-week randomized clinical trial.Journal of translational medicine · 2025Trial
- Gut-heart-kidney communication in cardiovascular disease: from a single-metabolite hypothesis to a context-dependent metabolite network.American journal of physiology. Heart and circulatory physiology · 2026Review
- Trimethylamine N-oxide and major adverse cardiac and cerebrovascular events: results of umbrella review and meta-analysis.Nutrition & metabolism · 2026Article
- The Gut-Heart Axis in Cardiovascular Disease: Microbial Metabolites, Mediterranean and Traditional Turkish Dietary Patterns, and Personalized Medicine.International journal of molecular sciences · 2026Review
- The Gut-Heart-Kidney Axis in Heart Failure: Trimethylamine N-Oxide and Beyond-A State-of-the-Art Review.Biomedicines · 2026Review
- From Fecal Microbial Potential to Circulating Trimethylamine N-oxide and Cardiovascular Events: A Narrative Review.Cureus · 2026Review
- Trimethylamine N-Oxide, a Bariatric Surgery-Associated Host-Microbial Cometabolite, Reduces Colonic Tumorigenesis in a Sex-Dependent Manner.Cellular and molecular gastroenterology and hepatology · 2026Article
- Article
- Gut microbiota and renal fibrosis: novel mechanistic insights and therapeutic potential.Acta pharmacologica Sinica · 2026Review
- Trimethylamine N-oxide as a key microbial mediator in the progression of diabetic kidney disease.World journal of nephrology · 2026Article
- Extraintestinal Manifestations of Inflammatory Bowel Disease: A Focus on Kidney Complications.International journal of molecular sciences · 2026Review
- [Mechanisms of gutZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- TMAO Induced Kidney Aging by Activating ZBP1-Mediated Necroptosis.Physiological research · 2026Article
- A gut microbiome-kidney-heart axis predictive of future cardiovascular diseases.Nature communications · 2026Article
- Gut microbial-derived metabolites: key players in kidney disease and renal fibrosis.International journal of biological sciences · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
47 authors at 20 institutions in 9 countries.
Petros Andrikopoulos *Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. p.andrikopoulos04@imperial.ac.uk.ORCID http://orcid.org/0000-0002-1555-3498
Judith Aron-Wisnewsky *Sorbonne Université, INSERM, Nutrition and obesities; systemic approaches (NutriOmics), Paris, France.
Rima Chakaroun *Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.
Antonis Myridakis *Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-1690-6651
Sofia K Forslund *Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-4285-6993
Trine NielsenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-2066-7895
Solia AdriouchSorbonne Université, INSERM, Nutrition and obesities; systemic approaches (NutriOmics), Paris, France.
Bridget HolmesDanone Research, Palaiseau, France.
Julien ChillouxSection of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-0384-7317
Sara Vieira-SilvaLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-4616-7602
Gwen FalonyLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-2450-0782
Joe-Elie SalemAssistance Publique Hôpitaux de Paris, Pitie-Salpêtrière Hospital, Paris, France.ORCID http://orcid.org/0000-0002-0331-3307
Fabrizio AndreelliSorbonne Université, INSERM, Nutrition and obesities; systemic approaches (NutriOmics), Paris, France.
Eugeni BeldaSorbonne Université, INSERM, Nutrition and obesities; systemic approaches (NutriOmics), Paris, France.
Julius KieswichDiabetic Kidney Disease Centre, Renal Unit, Barts Health National Health Service Trust, The Royal London Hospital, London, UK.
Kanta ChechiSection of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-1929-4128
Francesc Puig-CastellviEuropean Genomics Institute for Diabetes, EGENODIA, INSERM U1283, CNRS UMR8199, Institut Pasteur de Lille, Lille University Hospital, University of Lille, Lille, France.ORCID http://orcid.org/0000-0003-1064-9586
Mickael ChevalierEuropean Genomics Institute for Diabetes, EGENODIA, INSERM U1283, CNRS UMR8199, Institut Pasteur de Lille, Lille University Hospital, University of Lille, Lille, France.
Emmanuelle Le ChatelierMetagenopolis, INRA, AgroParisTech, Université Paris-Saclay, Paris, France.ORCID http://orcid.org/0000-0002-2724-0536
Michael T OlanipekunSection of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-7844-0370
Lesley HoylesDepartment of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, UK.
Renato AlvesStructural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-7212-0234
Gerard HelftAssistance Publique Hôpitaux de Paris, Pitie-Salpêtrière Hospital, Paris, France.
Richard IsnardSorbonne Université, INSERM, Nutrition and obesities; systemic approaches (NutriOmics), Paris, France.
Lars KøberDepartment of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-6635-1466
Luis Pedro CoelhoStructural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.
Christine RouaultSorbonne Université, INSERM, Nutrition and obesities; systemic approaches (NutriOmics), Paris, France.
Dominique GauguierINSERM UMR 1124, Université de Paris, 45 rue des Saint-Pères, 75006, Paris, France.ORCID http://orcid.org/0000-0001-6156-9530
Jens Peter GøtzeDepartment of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Edi PriftiSorbonne Université, INSERM, Nutrition and obesities; systemic approaches (NutriOmics), Paris, France.ORCID http://orcid.org/0000-0001-8861-1305
Philippe FroguelEuropean Genomics Institute for Diabetes, EGENODIA, INSERM U1283, CNRS UMR8199, Institut Pasteur de Lille, Lille University Hospital, University of Lille, Lille, France.
MetaCardis Consortium
Jean-Daniel ZuckerSorbonne Université, INSERM, Nutrition and obesities; systemic approaches (NutriOmics), Paris, France.ORCID http://orcid.org/0000-0002-5597-7922
Fredrik BäckhedThe Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Henrik VestergaardNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-3090-269X
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-8748-3831
Jean-Michel OppertAssistance Publique Hôpitaux de Paris, Pitie-Salpêtrière Hospital, Paris, France.
Matthias BlüherMedical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.
Jens NielsenDepartment of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Jeroen RaesLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-1337-041X
Peer BorkStructural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-2627-833X
Muhammad M YaqoobDiabetic Kidney Disease Centre, Renal Unit, Barts Health National Health Service Trust, The Royal London Hospital, London, UK.
Michael StumvollMedical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.ORCID http://orcid.org/0000-0001-6225-8240
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-3321-3972
S Dusko EhrlichDepartment of Clinical and Movement Neurosciences, University College London, London, NW3 2PF, UK.
Karine ClémentSorbonne Université, INSERM, Nutrition and obesities; systemic approaches (NutriOmics), Paris, France. karine.clement@inserm.fr.
Marc-Emmanuel DumasSection of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. m.dumas@imperial.ac.uk.ORCID http://orcid.org/0000-0001-9523-7024
Inserm · FRSorbonne Université · FRUniversity of Copenhagen · DKAgroParisTech · FREuropean Molecular Biology Laboratory · DEImperial College London · GBCentre National de la Recherche Scientifique · FRJohannes Gutenberg University Mainz · DEMax Delbrück Center · DENational Health Service · GBCentre de Coopération Internationale en Recherche Agronomique pour le Développement · FRChalmers University of Technology · SEDanone (France) · FRLung Institute · USMRC Centre for Environment and HealthNottingham Trent University · GBRega Institute for Medical Research · BEUniversity College London · GBUniversity of Gothenburg · SEYonsei University · KR
Funding
Medical Research Council MR/S019669/1
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.
Indexed as
EndocrinologyMethylaminesAdultCausalityHumansKidneyMethylaminestrimethyloxamine
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