• Vance L Albaugh, Charles Robb Flynn, Steven Cai, Yi Xiao, Robyn A Tamboli, and Naji N Abumrad.
• Department of Surgery (V.L.A., C.R.F., R.A.T., N.N.A.), Vanderbilt University Medical Center, Nashville, Tennessee 37232; Rosalind Franklin University (S.C.), North Chicago, Illinois 60064; and Department of Biochemistry (Y.X.), Vanderbilt University Medical Center, Nashville, Tennessee 37232.
• J. Clin. Endocrinol. Metab. 2015 Sep 1; 100 (9): E1225-33.

ContextRoux-en-Y gastric bypass (RYGB) is the most effective treatment for morbid obesity and resolution of diabetes. Over the last decade, it has become well accepted that this resolution of diabetes occurs before significant weight loss; however, the mechanisms behind this effect remain unknown and could represent novel therapeutic targets for obesity and diabetes. Bile acids have been identified as putative mediators of these weight loss-independent effects.ObjectiveTo identify the longitudinal changes in bile acids after RYGB, which may provide mechanistic insight into the weight loss-independent effects of RYGB.DesignObservational study before/after intervention.SettingAcademic medical center.Patients/ParticipantsSamples were collected from morbidly obese patients (n = 21) before and after RYGB.InterventionRYGB.Main Outcome MeasuresSeventeen individual bile acid species were measured preoperatively and at 1, 6, 12, and 24 months postoperatively. Anthropometric, hormonal, and hyperinsulinemic-euglycemic clamp data were also examined to identify physiological parameters associated with bile acid changes.ResultsFasting total plasma bile acids increased after RYGB; however, increases were bimodal and were observed only at 1 (P < .05) and 24 months (P < .01). One-month increases were secondary to surges in ursodeoxycholic acid and its glycine and taurine conjugates, bacterially derived bile acids with putative insulin-sensitizing effects. Increases at 24 months were due to gradual rises in primary unconjugated bile acids as well as deoxycholic acid and its glycine conjugate. Plasma bile acid changes were not significantly associated with any anthropometric or hormonal measures, although hepatic insulin sensitivity was significantly improved at 1 month.ConclusionsOverall findings suggest that bacterially derived bile acids may mediate the early improvements at 1 month after RYGB. Future studies should examine the changes in specific bile acid chemical species after bariatric procedures and bile acid-specific signaling changes.

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