title: Metabolomic fingerprint of severe obesity is dynamically affected by bariatric surgery in a procedure-dependent manner.
abstract: BACKGROUND
  Obesity is associated with multiple diseases. Bariatric surgery is the most effective therapy for severe obesity that can reduce body weight and obesity-associated morbidity. The metabolic alterations associated with obesity and respective changes after bariatric surgery are incompletely understood.
  
  
  OBJECTIVE
  We comprehensively assessed metabolic alterations associated with severe obesity and distinct bariatric procedures.
  
  
  METHODS
  In our longitudinal observational study, we applied a (1)H-nuclear magnetic resonance-based global, untargeted metabolomics strategy on human serum samples that were collected before and repeatedly ≤1 y after distinct bariatric procedures [i.e., a sleeve gastrectomy, proximal Roux-en Y gastric bypass (RYGB), and distal RYGB]. For comparison, we also analyzed serum samples from normal-weight and less-obese subjects who were matched for 1-y postoperative body mass index (BMI) values of the surgical groups.
  
  
  RESULTS
  We identified a metabolomic fingerprint in obese subjects that was clearly discriminated from that of normal-weight subjects. Furthermore, we showed that bariatric surgery (sleeve gastrectomy and proximal and distal RYGB) dynamically affected this fingerprint in a procedure-dependent manner, thereby establishing new fingerprints that could be discriminated from those of BMI-matched and normal-weight control subjects. Metabolites that largely contributed to the metabolomic fingerprints of severe obesity were aromatic and branched-chain amino acids (elevated), metabolites related to energy metabolism (pyruvate and citrate; elevated), and metabolites suggested to be derived from gut microbiota (formate, methanol, and isopropanol; all elevated).
  
  
  CONCLUSIONS
  Our data indicate that bariatric surgery, irrespective of the specific kind of procedure used, reverses most of the metabolic alterations associated with obesity and suggest profound changes in gut microbiome-host interactions after the surgery. This trial was registered at clinicaltrials.gov as NCT02480322.
authors.affiliation: FiorGen Foundation, Sesto Fiorentino, Italy; Magnetic Resonance Center and.
authors.forename: Ewa
authors.initials: E
authors.lastname: Gralka
authors.affiliation: Magnetic Resonance Center and Chemistry Department, University of Florence, Sesto Fiorentino, Italy; and.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.affiliation: FiorGen Foundation, Sesto Fiorentino, Italy;
authors.forename: Leonardo
authors.identifier: http://orcid.org/0000-0001-6438-059X
authors.initials: L
authors.lastname: Tenori
authors.affiliation: eSwiss Medical & Surgical Center, Interdisciplinary Obesity Center, St. Gallen, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ernst
authors.affiliation: eSwiss Medical & Surgical Center, Interdisciplinary Obesity Center, St. Gallen, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Thurnheer
authors.affiliation: eSwiss Medical & Surgical Center, Interdisciplinary Obesity Center, St. Gallen, Switzerland bernd.schultes@stephanshorn.ch.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schultes
mesh_terms: D000328:Adult; D024322:Amino Acids, Aromatic / Q000097:blood* / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000097:blood* / Q000378:metabolism; D001771:Blood Banks; D015992:Body Mass Index; D019343:Citric Acid / Q000097:blood* / Q000378:metabolism; D016002:Discriminant Analysis; D005260:Female; D015390:Gastric Bypass / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D016555:Matched-Pair Analysis; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009010:Monte Carlo Method; D009765:Obesity / Q000097:blood / Q000378:metabolism; D009767:Obesity, Morbid / Q000097:blood* / Q000378:metabolism / Q000601:surgery; D019289:Pyruvic Acid / Q000097:blood* / Q000378:metabolism; D013557:Switzerland; D015854:Up-Regulation
chemical_list: D024322:Amino Acids, Aromatic; D000597:Amino Acids, Branched-Chain; D019343:Citric Acid; D019289:Pyruvic Acid
keywords: NMR spectroscopy; Roux-en Y gastric bypass; metabolomics; metabonomics; sleeve gastrectomy