The exact impact of bariatric surgery in metabolically "healthy" (MH) or "unhealthy" (MU) phenotypes for the study of the metabolic improvement is still unknown. We applied an untargeted LC-ESI-TripleTOF-MS-driven metabolomics approach in serum samples from 39 patients with morbid obesity (MH and MU) 1, 3, and 6 months after bariatric surgery. Multiple factor analysis, along with correlation and enrichment analyses, was carried out to distinguish those metabolites associated with metabolic improvement. Hydroxypropionic acids, medium-/long-chain hydroxy fatty acids, and bile acid glucuronides were the most discriminative biomarkers of response between MH and MU phenotypes. Hydroxypropionic (hydroxyphenyllactic-related) acids, amino acids, and glycerolipids were the most significant clusters of metabolites altered after bariatric surgery in MU ( p < 0.001). After surgery, MU and MH changed toward a common metabolic state 3 months after surgery. We observed a negative correlation with changes in waist circumference and cholesterol levels with metabolites of lipid metabolism. Glycemic variables were correlated with hexoses, which, in turn, correlated with gluconic acid and amino acid metabolism. Finally, we noted that hydroxyphenyllactic acid was associated with amino acid and lipid metabolism. Microbial metabolism of amino acid and BA glucuronidation pathways may be the key points of metabolic rearrangement after surgery.
Keywords: bariatric surgery; hydroxyphenyllactic; indole metabolites; mass spectrometry; metabolically healthy; microbiota metabotype; obesity; untargeted metabolomics.