Serum and Urinary Metabolomics Reflect the Early Stages of De Novo Metabolic Syndrome After Liver Transplant: A 2-Center Longitudinal Study

INTRODUCTION: Liver transplantation (LT) recipients are at high risk of developing de novo metabolic syndrome (MetS), which contributes to cardiovascular and cerebrovascular morbidity. This study investigated serum and urinary metabolic changes after LT to identify microbial and metabolic markers associated with MetS development. METHODS: We conducted a prospective, 2-center longitudinal study with biospecimen collection pre-LT and at 6 months, 1 year, and 2-9 years post-LT. Nuclear magnetic resonance spectroscopy was used to characterize serum and urine metabolomic profiles from 73 to 44 patients, respectively. MetS was defined as body mass index >30 kg/m 2 plus at least 1 additional metabolic abnormality. RESULTS: MetS prevalence increased from 11% pre-LT to 36% post-LT. Post-LT, serum metabolite profiles showed increased phosphocholines and lipid-CH 3 (low density lipoprotein), whereas urine profiles demonstrated higher levels of trimethylamine- N -oxide (TMAO) and phenylacetylglutamine. Patients who developed or had persistent MetS exhibited smaller increases in serum phosphocholines and lipid-CH 3 but greater elevations in urinary TMAO levels compared with patients who remained MetS-free. DISCUSSION: LT is followed by distinct metabolic shifts reflecting changes in both hepatic lipid metabolism and gut-liver microbial cometabolism. Elevated urinary TMAO, together with reduced serum phosphocholine and lipid-CH 3 responses, characterize patients who develop post-LT MetS and may serve as early biomarkers of cardiometabolic risk in LT recipients.