Elevated urinary TMAO, together with reduced serum phosphocholine and lipid-CH3 responses, characterize patients who develop post-LT MetS and may serve as early biomarkers of cardiometabolic risk in LT recipients.
Key Findings
Results
Metabolic syndrome prevalence increased substantially from pre-transplant to post-transplant periods.
MetS prevalence increased from 11% pre-LT to 36% post-LT.
MetS was defined as body mass index >30 kg/m2 plus at least 1 additional metabolic abnormality.
The study was a prospective, 2-center longitudinal study with biospecimen collection pre-LT and at 6 months, 1 year, and 2-9 years post-LT.
Serum metabolomic profiles were characterized from 73 patients and urinary profiles from 44 patients using nuclear magnetic resonance spectroscopy.
Results
Post-LT serum metabolite profiles showed increased phosphocholines and lipid-CH3 (low density lipoprotein) levels.
Nuclear magnetic resonance spectroscopy was used to characterize serum metabolomic profiles from 73 patients.
Increased serum phosphocholines and lipid-CH3 were identified as distinct post-LT metabolic shifts.
These changes were interpreted as reflecting changes in hepatic lipid metabolism following liver transplantation.
Results
Post-LT urine metabolite profiles demonstrated higher levels of trimethylamine-N-oxide (TMAO) and phenylacetylglutamine.
Urinary metabolomic profiles were characterized from 44 patients using nuclear magnetic resonance spectroscopy.
Elevated TMAO and phenylacetylglutamine were identified in urine profiles post-LT.
These changes were interpreted as reflecting gut-liver microbial cometabolism changes following liver transplantation.
Results
Patients who developed or had persistent MetS exhibited smaller increases in serum phosphocholines and lipid-CH3 compared with MetS-free patients.
Patients were categorized as those who developed or had persistent MetS versus those who remained MetS-free.
MetS patients showed smaller increases in serum phosphocholines post-LT compared to MetS-free patients.
MetS patients also showed smaller increases in lipid-CH3 (LDL) post-LT compared to MetS-free patients.
These reduced serum metabolite responses were identified as characterizing the MetS phenotype post-LT.
Results
Patients who developed or had persistent MetS exhibited greater elevations in urinary TMAO levels compared with MetS-free patients.
Greater urinary TMAO elevations were observed in MetS patients compared to MetS-free patients post-LT.
Elevated urinary TMAO was identified as a potential early biomarker of cardiometabolic risk in LT recipients.
TMAO elevation was interpreted as reflecting gut-liver microbial cometabolism differences between MetS and non-MetS patients.
Discussion
LT is followed by distinct metabolic shifts reflecting changes in both hepatic lipid metabolism and gut-liver microbial cometabolism.
The study identified two categories of metabolic change post-LT: hepatic lipid metabolism changes (reflected by serum phosphocholines and lipid-CH3) and gut-liver microbial cometabolism changes (reflected by urinary TMAO and phenylacetylglutamine).
These metabolic shifts were characterizable using nuclear magnetic resonance spectroscopy of serum and urine samples.
The pattern of these metabolic shifts differed between patients who did and did not develop MetS.
Cox I, Lauridsen M, Le Guennec A, Fagan A, Heitmann G, Lukose T, et al.. (2026). Serum and Urinary Metabolomics Reflect the Early Stages of De Novo Metabolic Syndrome After Liver Transplant: A 2-Center Longitudinal Study.. Clinical and translational gastroenterology. https://doi.org/10.14309/ctg.0000000000000968