"Omics" Prospective Monitoring of Bariatric Surgery: Roux-En-Y Gastric Bypass Outcomes Using Mixed-Meal Tolerance Test and Time-Resolved (1)H NMR-Based Metabolomics

Abstract

Roux-en-Y gastric bypass (RYGB) surgery goes beyond weight loss to induce early beneficial hormonal changes that favor glycemic control. In this prospective study, ten obese subjects diagnosed with type 2 diabetes underwent bariatric surgery. Mixed-meal tolerance test was performed before and 12 months after RYGB, and the outcomes were investigated by a time-resolved hydrogen nuclear magnetic resonance ((1)H NMR)-based metabolomics. To the best of our knowledge, no previous omics-driven study has used time-resolved (1)H NMR-based metabolomics to investigate bariatric surgery outcomes. Our results presented here show a significant decrease in glucose levels after bariatric surgery (from 159.80 ± 61.43 to 100.00 ± 22.94 mg/dL), demonstrating type 2 diabetes remission (p < 0.05). The metabolic profile indicated lower levels of lactate, alanine, and branched chain amino acids for the operated subject at fasting state after the surgery. However, soon after food ingestion, the levels of these metabolites increased faster in operated than in nonoperated subjects. The lipoprotein profile achieved before and after RYGB at fasting was also significantly different, but converging 180 min after food ingestion. For example, the very low-density lipoprotein, low-density lipoprotein, N-acetyl-glycoproteins, and unsaturated lipid levels decreased after RYGB, while phosphatidylcholine and high-density lipoprotein increased. This study provides important insights on RYGB surgery and attendant type 2 diabetes outcomes using an "omics" systems science approach. Further research on metabolomic correlates of RYGB surgery in larger study samples is called for.

FIG. 1.

(A) T₂-edited and (B) diffusion-edited ¹H NMR spectrum model for overweight subjects before RYGB. ¹H NMR, hydrogen nuclear magnetic resonance; RYGB, Roux-en-Y gastric bypass.

FIG. 2.

(A) Scores plot for two first factors of the NPLS-DA model from T₂-edited ¹H NMR data; (B') first spectral loading from NPLS-DA model; (B) T₂-edited ¹H NMR spectra model; and (C) first temporal loading from NPLS-DA model. 1, isoleucine; 2, leucine; 3, valine; 4, lactate; 5, alanine; and 6, glucose. Calibration samples from patients (+) before and () after RYGB. Validation samples from patients (x) before and () after RYGB. NPLS-DA, N-way partial least squares discriminant analysis.

FIG. 3.

(A) Scores plot for two first factors of the NPLS-DA model from diffusion-edited ¹H NMR data; (B') first spectral loading from the NPLS-DA model; (B) diffusion-edited ¹H NMR spectra model; and (C) first temporal loading of the NPLS-DA model. Calibration samples from patients (+) before and () after RYGB. Validation samples from patients (x) before and () after RYGB. PtoCho, phosphatidylcholine.

FIG. 4.

Trajectories of the postprandial states, shown as fold changes compared to the baseline levels of (A) glucose; (B) lactate; (C) valine; (D) leucine/isoleucine; and (E) alanine. (■) before and () after RYGB.

FIG. 5.

Trajectories of the postprandial states, shown as fold changes compared to the baseline levels of (A) VLDL; (B) LDL; and (C) HDL. (■) before and () after RYGB. HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein.