Abstract Introduction Predicting success after bariatric surgery remains a challenge when relying solely on BMI or diabetes status. We aimed to show that detailed metabolic phenotyping could identify which patients truly benefit from surgery and guide targeted preoperative care. Methodology We conducted a multicentre, prospective cross-sectional study (ClinicalTrials.gov NCT05322551, Malaysia Research Ethics MREC NMRR-20-2496-56353) involving 185 patients from four Malaysian tertiary hospitals, all scheduled for metabolic surgery (either RYGB or LSG). Each participant had a preoperative NMR metabolomics panel measuring 47 metabolites. Using cluster analysis, we grouped patients by metabolic phenotype and linked these profiles to weight loss, diabetes remission, and liver enzyme recovery over 12 months. Statistical models included ANOVA, regression, and ROC analysis, with all confidence intervals reported at 95%. Results Patients clustered into four clear metabolic subtypes:About 39% had a BCAA-dominant profile, marked by significantly elevated valine and leucine, and a notably high baseline BMI averaging 46.1 kg/m2.Roughly 26% fell into a TMAO/glycine-impaired group, defined by markedly raised TMAO (over twice the healthy reference) and low glycine.Another 24% were “ketogenic,” with strong elevations in 3-hydroxybutyrate and fucose.The smallest group, about 11%, showed an inflammatory signature with low glutamine and high hydroxyacetone. Outcomes varied strikingly by metabolic phenotype. The BCAA-dominant group achieved the best results, with an average excess weight loss of 82.7%—more than 14% higher than any other group (P 0.001). TMAO/glycine-impaired patients had the lowest weight loss, averaging 68.3%, despite a lower starting BMI. Diabetes remission also followed this pattern. BCAA-dominant patients had a 68% remission rate and were over three times as likely to achieve remission compared to those with TMAO/glycine impairment (OR 3.1, 95% c.i.: 1.8–5.4). Remission rates were intermediate in the ketogenic (63%) and inflammatory (49%) groups. Liver recovery, as measured by ALT reduction, was strongest in the ketogenic group (mean reduction of 31%), whereas the TMAO/glycine group lagged behind (18% reduction; P = 0.007). Among diabetic patients, improvements in ALT closely tracked weight loss (Spearman’s rho 0.86, q 0.001). Patients with higher glycine normalized their ESM-1 levels two and a half times faster than those who were glycine-deficient (HR 2.51, P = 0.003). Predictive modelling supported these findings: TMAO levels above 150 µM predicted a poor ALT response with an AUC of 0.91. A composite BCAA score identified super-responders for weight loss with an AUC of 0.88, and low glycine flagged delayed endothelial recovery (AUC 0.83). Clinical translation This metabolic approach is actionable. BCAA-high patients achieved 82.7% EWL when prioritized for LSG. TMAO-high patients benefited from a three-month preoperative “gut reset,” which improved their ALT reduction from 18% to 28% (P = 0.01). Supplementing glycine in deficient patients cut recovery time for ESM-1 normalization by more than half. Conclusion Metabolic phenotyping provides a level of precision that conventional stratification simply cannot match. It reliably identifies “super-responders,” flags those at risk of poor liver recovery, and enables tailored pre-op optimization. This approach led to a 27% absolute increase in diabetes remission rates compared to standard practice (95% c.i.: 19–35%, P 0.001), all while using objective, accessible biomarkers. In summary, metabolic signatures can guide smarter surgery and transform patient outcomes.
Gee et al. (Thu,) studied this question.