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 < .001), whereas
TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (
p = .44). After liver transplantation (
n = 13), betaine decreased (
p = .017;
p = .36 vs. PREVEND population), whereas
TMAO levels tended to increase (
p = .085) to higher levels than in the PREVEND population (
p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both
p < .001). The association with the MELD score remained in the fully adjusted analysis (
p < .001). The association of
TMAO with the MELD score did not reach significance (
p = .11). Neither betaine nor
TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted
p = .78 and
p = .44, respectively).
Conclusion
Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation.
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