(P31-005-23) Sleeve Gastrectomy and Gastric Bypass Surgeries Have Differing Effects on Plasma Metabolomic Profiles

Objectives: Gastric bypass and sleeve gastrectomy surgeries are associated with differences in weight loss and metabolic outcomes, but the mechanisms are incompletely understood. This study used metabolomics to probe the effects of two types of bariatric surgery on plasma metabolite profiles.

Methods: Our study included obese adults from a prospective cohort of bariatric surgery who underwent either sleeve gastrectomy or gastric bypass surgery and were screened preoperatively and at 3 and 12 months post-operatively. Plasma metabolomics data were assessed for 104 participants at baseline, 98 at 3 and 78 at 12 months post-surgery. Global metabolomic profiles comprising a total of 1268 biochemicals were determined using Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS) at Metabolon. Multivariable linear mixed-effects models were used to test for associations between changes in metabolite levels and surgery type over 3 time points.

Results: The mean age of participants in the gastric bypass (n=27) and sleeve gastrectomy (n=77) groups were 42.48±12.6 and 43.56±12.49 years, respectively. Mean starting BMI was 46.45 (IQR, 40.68-49.98) in the gastric bypass and 43.8 (IQR, 40.77-48.28) in the sleeve gastrectomy groups. As baseline total cholesterol, hemoglobin A1c and baseline diabetes status significantly (P < 0.05) differed between these two groups, these variables were adjusted for in all multivariable models. Findings from multivariable linear mixed-effects models showed that gastric bypass, compared to sleeve gastrectomy, was associated with (at the false discovery rate (FDR) p-value < 0.05) greater increases in levels of a secondary bile acid (glycohyocholate), three primary bile acids (glyco-beta-muricholate, cholic acid glucuronide and cholate) and an unknown compound (X-11315). The most significant differentially modulated metabolite by surgery type was glycohyocholate (ß=-0.59 [standard error=0.13], p= 0.005) which showed 376.6% increase in gastric bypass vs. 61.22% increase in sleeve gastrectomy at 12 months post-surgery.

Conclusions: Our findings highlighted differences in plasma bile acid profiles following bariatric surgery, with greater increases in bile acids following gastric bypass when compared with sleeve gastrectomy.

Funding Sources: R01 HL142856