Exploring the trimethylamine pathway in advanced chronic liver disease

Abstract The trimethylamine (TMA)-trimethylamine-N-oxide (TMAO) pathway, involving gut microbiota-derived metabolites, may play a role in advanced chronic liver disease (ACLD). This study assessed TMA and TMAO levels in ACLD patients and their associations with liver-related outcomes. Plasma samples...

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Main Authors: Jil T. Bürki, Jonas Schropp, Peter Neyer, Christian Steuer, Jaume Bosch, Annalisa Berzigotti, Susana G. Rodrigues
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Gut and Liver
Online Access:https://doi.org/10.1038/s44355-025-00029-9
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author Jil T. Bürki
Jonas Schropp
Peter Neyer
Christian Steuer
Jaume Bosch
Annalisa Berzigotti
Susana G. Rodrigues
author_facet Jil T. Bürki
Jonas Schropp
Peter Neyer
Christian Steuer
Jaume Bosch
Annalisa Berzigotti
Susana G. Rodrigues
author_sort Jil T. Bürki
collection DOAJ
description Abstract The trimethylamine (TMA)-trimethylamine-N-oxide (TMAO) pathway, involving gut microbiota-derived metabolites, may play a role in advanced chronic liver disease (ACLD). This study assessed TMA and TMAO levels in ACLD patients and their associations with liver-related outcomes. Plasma samples from 66 ACLD patients (30 compensated, 36 decompensated) and 11 healthy controls were analyzed using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry LC-MS/MS. Associations with clinical outcomes: hepatic decompensation, hepatocellular carcinoma, acute kidney injury, liver transplantation or death, and major cardiovascular events, were assessed using statistical models.TMAO levels were slightly elevated in ACLD patients, but not significantly different from controls (p = 0.649). The TMAO/TMA ratio negatively correlated with Child-Pugh score (r = −0.31, p = 0.02). Higher TMA levels were associated with increased risk of liver-related events (HR: 1.36; p = 0.003).TMA, rather than TMAO, may serve as a prognostic marker in ACLD. Further research is needed to elucidate its role in disease progression and therapeutic potential.
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spelling doaj-art-e169430a68a6419d9e432a87d85ac3022025-08-20T04:01:53ZengNature Portfolionpj Gut and Liver3004-98062025-07-01211710.1038/s44355-025-00029-9Exploring the trimethylamine pathway in advanced chronic liver diseaseJil T. Bürki0Jonas Schropp1Peter Neyer2Christian Steuer3Jaume Bosch4Annalisa Berzigotti5Susana G. Rodrigues6Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department for BioMedical Research, Visceral Surgery and Medicine, University of BernDepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department for BioMedical Research, Visceral Surgery and Medicine, University of BernInstitute of Laboratory Medicine, Kantonsspital AarauInstitute of Pharmaceutical Sciences, ETHDepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department for BioMedical Research, Visceral Surgery and Medicine, University of BernDepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department for BioMedical Research, Visceral Surgery and Medicine, University of BernDepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department for BioMedical Research, Visceral Surgery and Medicine, University of BernAbstract The trimethylamine (TMA)-trimethylamine-N-oxide (TMAO) pathway, involving gut microbiota-derived metabolites, may play a role in advanced chronic liver disease (ACLD). This study assessed TMA and TMAO levels in ACLD patients and their associations with liver-related outcomes. Plasma samples from 66 ACLD patients (30 compensated, 36 decompensated) and 11 healthy controls were analyzed using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry LC-MS/MS. Associations with clinical outcomes: hepatic decompensation, hepatocellular carcinoma, acute kidney injury, liver transplantation or death, and major cardiovascular events, were assessed using statistical models.TMAO levels were slightly elevated in ACLD patients, but not significantly different from controls (p = 0.649). The TMAO/TMA ratio negatively correlated with Child-Pugh score (r = −0.31, p = 0.02). Higher TMA levels were associated with increased risk of liver-related events (HR: 1.36; p = 0.003).TMA, rather than TMAO, may serve as a prognostic marker in ACLD. Further research is needed to elucidate its role in disease progression and therapeutic potential.https://doi.org/10.1038/s44355-025-00029-9
spellingShingle Jil T. Bürki
Jonas Schropp
Peter Neyer
Christian Steuer
Jaume Bosch
Annalisa Berzigotti
Susana G. Rodrigues
Exploring the trimethylamine pathway in advanced chronic liver disease
npj Gut and Liver
title Exploring the trimethylamine pathway in advanced chronic liver disease
title_full Exploring the trimethylamine pathway in advanced chronic liver disease
title_fullStr Exploring the trimethylamine pathway in advanced chronic liver disease
title_full_unstemmed Exploring the trimethylamine pathway in advanced chronic liver disease
title_short Exploring the trimethylamine pathway in advanced chronic liver disease
title_sort exploring the trimethylamine pathway in advanced chronic liver disease
url https://doi.org/10.1038/s44355-025-00029-9
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