Abstract / Summary
Background We tested the primary hypothesis that lower continuous 24-hour urinary 6-sulfatoxymelatonin (6-SMT) is associated with an adverse lipid and inflammatory profile in adults with dyslipidemia. Associations with FGF19, bile-acid composition, and gut microbiome features were secondary and exploratory.Methods This prospectively enrolled, single-center cross-sectional study included 577 consecutive adults evaluated at the Institute for Personalized Medicine, Tbilisi, Georgia, during 2020–2025. Each participant completed three non-consecutive 24-hour urine collections. Validity required a measured-to-predicted creatinine-excretion ratio of 0.80–1.20, and the participant-level 6-SMT value was the arithmetic mean of three valid collections. Fasting lipids, hs-CRP, FGF19, bile-acid profiles, and 16S rRNA taxonomic composition were assessed. An internal method-matched but unmatched normolipidemic reference comparator (n = 120) was used only for descriptive analyses.Results Median 6-SMT was 8.4 μg/24 h (IQR 5.2–12.1). Lower 6-SMT was associated with higher LDL-C (Spearman ρ = −0.38; approximate 95% CI −0.45 to −0.31), triglycerides (ρ = −0.31; −0.38 to −0.23), and hs-CRP (ρ = −0.35; −0.42 to −0.28), and with lower HDL-C (ρ = 0.29; 0.21 to 0.36). FGF19 was above the stated fasting reference range in 489/577 participants (85%; median 312 pg/mL) and correlated inversely with 6-SMT (ρ=-0.42; −0.48 to −0.35). The emphasized microbial taxa correlated positively with 6-SMT. In a post hoc unadjusted statin-stratified sensitivity analysis, the mean difference in 6-SMT for statin users versus non-users was −0.30 μg/24 h (95% CI −0.83 to 0.23; p = 0.26). False-discovery-rate sensitivity analysis across the 14 reported reference-comparator microbiome tests retained q < 0.05 for each reported comparison; this does not resolve comparator confounding. The exploratory complete-case multivariable model had adjusted R2=0.40 but was not interpreted causally.Conclusions Lower 24-hour urinary 6-SMT clustered with adverse lipid and inflammatory measures and with exploratory enterohepatic and taxonomic microbiome features. The findings are hypothesis-generating and do not establish a coordinated biological axis, directionality, diagnostic utility, incremental predictive value, or treatment effect.