Impact of metabolic and bariatric surgery on the paediatric & adolescent metabolome: A systematic review and meta-analysis.

Metabolic bariatric surgery (MBS) is an effective treatment for paediatric obesity, yet the mechanisms underlying weight loss remain unclear. This systematic review and meta-analysis evaluated the short- and long-term effects of MBS on the paediatric metabolome to provide insights into metabolic pathways contributing to surgical outcomes. This prospectively registered systematic review (PROSPERO ID: CRD42024607784) adhered to PRISMA guidelines. Meta-analysis was undertaken on pre-defined post-operative weight and metabolic parameters in paediatric patients (aged 5- 19 years) following MBS. Outcomes were reported as weighted or standardised mean Difference with 95 percent confidence intervals from random effects modelling. Quality scoring and quantitative assessment of bias were performed. Results from 12 studies (451 patients, mean age 16.9 years) across five countries were included. The median follow-up was 12 months. Patients underwent Roux-en-Y gastric bypass (RYGB, n = 275) or laparoscopic sleeve gastrectomy (LSG, n = 140). Most studies used serum and urine assays; two included tissue biosamples. MBS was associated with significant long-term weight reduction, with a mean BMI decrease of -14.4 kg/m2 (95% CI: -17.5 to -11.3) and %TWL of 25% (95% CI: 18.6 to 32.2). Metabolic improvements included reduced cholesterol (-10 mg/dL), LDL (-14.6 mg/dL), triglycerides (-33.3 mg/dL), and increased HDL (+ 8.0 mg/dL). Significant enhancements were noted in glycaemic, pancreatic and insulin regulation, evidenced by decreased HOMA-IR (-4.1) and C-peptide (-1.8 ng/mL). Liver function parameters, ALT (-14.4 U/L), AST (-5.4 U/L), and GGT (-9.6 U/L) and inflammatory cytokines, IL-6 (-12.2 pg/mL) and TNF-α (-54 pg/mL) significantly declined following surgery. These findings demonstrate a distinct metabolic signature of MBS in adolescents, leading to substantial weight loss and improvements in cardiovascular, glycaemic, and liver health, alongside reduced systemic inflammation. These results underscore the efficacy of MBS as a therapeutic intervention for adolescents living with severe obesity, demonstrating a profound impact on the paediatric metabolome.