Multi-class urinary antibiotic exposure, dietary sources, and childhood overweight and obesity risk through lipid metabolic disruption: evidence from multicenter cohorts in China.

Given widespread antibiotic use and residues, this study examined associations of multi-class urinary antibiotic exposure with childhood overweight and obesity (OWOB) risk, identified potential dietary sources, and explored lipidomic signatures and potential indirect effects. We analyzed two cohorts from China: the 4C cohort (Inner Mongolia, 2024; n = 692) for diet-exposure analyses and the CBPEF cohort (Xiamen, 2018/2020; n = 594) for repeated-measures exposure-adiposity and lipidomics analyses. Twenty-four urinary antibiotics across six classes were measured by LC-MS/MS. BMI percentile, OWOB, and untargeted serum lipidomics were assessed, with lipidomics performed in a CBPEF subsample of 73 children. Multi-class antibiotic exposure and co-exposure were common in both cohorts, with >94% of children in the 4C cohort and ≥98% in the CBPEF cohort having at least two detected antibiotics. In the 4C cohort, fish/seafood intake was associated with higher detection of sulfonamides, tetracyclines, and quinolones, with the strongest diet-exposure association observed for seafood intake and sulfonamide detection (OR = 2.17, 95% CI: 1.05-4.48), whereas plant-based intake was inversely associated with total detected antibiotic counts (β = -0.492). In the CBPEF cohort, each additional antibiotic detected was associated with a 0.63-point increase in BMI percentile (95% CI: 0.34-0.92), and each additional human antibiotic detected was associated with 14% higher odds of OWOB (OR = 1.14, 95% CI: 1.04-1.24). Cumulative sulfonamide, quinolone, macrolide, tetracycline, and phenicol counts were positively associated with BMI percentile (β range: 1.15-2.45). Lipidomic analyses identified 102 candidate lipids shared by urinary antibiotic exposure metrics and BMI percentile, with PC1-based indirect-effect signals across multiple antibiotic classes and pathway annotations mainly involving steroid/cholesterol-related metabolism. These findings suggest that contemporary Chinese children and adolescents commonly experience multi-class antibiotic exposure, particularly involving quinolones and macrolides, which may partly reflect dietary and environmental sources and contribute to childhood obesity risk, with lipidomic signatures suggesting involvement of steroid/cholesterol-related metabolism.