High plasma levels of betaine, a trimethylamine N‐Oxide‐related metabolite, are associated with the severity of cirrhosis

Background and Aims The gut microbiome‐related metabolites betaine and trimethylamine N‐oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine...

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Bibliographic Details
Published in:Liver international 2023-02, Vol.43 (2), p.424-433
Main Authors: Berg, Eline H., Flores‐Guerrero, Jose L., Garcia, Erwin, Connelly, Margery A., Meijer, Vincent E., Bakker, Stephan J. L., Blokzijl, Hans, Dullaart, Robin P. F.
Format: Article
Language:English
Subjects:
Betaine
Betaine - metabolism
Betaine-homocysteine S-methyltransferase
Biomarkers
Cirrhosis
Cirrhosis, Liver Failure and Transplantation
Cohort analysis
Cohort Studies
CPT classification
End Stage Liver Disease
Flavin
Homocysteine
Humans
Intestinal microflora
Liver
Liver Cirrhosis
Liver diseases
Liver transplantation
Magnetic resonance spectroscopy
MELD score
Metabolism
Metabolites
Methyltransferase
Microbiomes
NMR
NMR spectroscopy
Nuclear magnetic resonance
Original
orthotopic liver transplantation
Plasma
Plasma levels
Severity of Illness Index
TMAO
Transplantation
Trimethylamine
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Summary:Background and Aims The gut microbiome‐related metabolites betaine and trimethylamine N‐oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end‐stage liver disease and assessed their relationships with liver disease severity. Methods Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child‐Pugh‐Turcotte (CPT) classification and Model for End‐stage Liver Disease (MELD) score. Results Plasma betaine was on average 60% higher (p 
ISSN:1478-3223
1478-3231
DOI:10.1111/liv.15310