Changes in Bile Acid Metabolism and Nutrient-Stimulated Hormone Responses After Malabsorptive Metabolic Surgery: RYGB Versus SADI-S
6 affiliations
- 1Department of Endocrinology and Nutrition, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
- 2Department of Clinical Analysis, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
- 3Department of General Surgery, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
- 4Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
- 5Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain
- 6Department of Nuclear Medicine, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
Abstract
Background/Objectives: Bariatric–metabolic surgery (BMS) improves obesity through neuroendocrine mechanisms involving bile acids (BAs) and nutrient-stimulated gastrointestinal hormones. However, the underlying pathophysiology involved remains poorly understood. BAs are essential for the digestion and absorption of dietary fat and fat-soluble vitamins and act as nutrient-responsive signaling molecules, so their handling after malabsorptive procedures is relevant both to metabolic outcomes and to nutritional status. Methods: We prospectively compared Roux-en-Y gastric bypass (RYGB) and single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) in a single-center case-control study including 37 RYGB and 31 SADI-S patients with severe obesity and 19 non-obese controls. Before and one year after surgery, participants underwent a standardized mixed-meal test (nutrient challenge) with measurement of 14 individual BA fractions, insulin, GLP-1, ghrelin, FGF19, leptin, and adiponectin; bile acid malabsorption was assessed one year after surgery with the 75Se-SeHCAT test, and weight was followed for up to 5 years. Results: Fasting total BAs increased after both techniques, with no significant between-technique difference in total BA exposure (primary outcome). The techniques were associated with distinct BA profiles: fasting concentrations of conjugated BAs (GCA, GCDCA, and TDCA) were higher after SADI-S than after RYGB (FDR-adjusted q < 0.05), with a similar but more variable pattern in postprandial AUCs, whereas RYGB was characterized by a greater postprandial rise in the unconjugated secondary BA DCA. After surgery, FGF19 increased progressively during the mixed-meal test, peaking at 90 min, and its increase correlated with the rise in conjugated BAs, particularly in SADI-S. The postprandial insulin peak shifted earlier in both techniques, with a lower insulin AUC in SADI-S; GLP-1 responses were supraphysiological, and ghrelin increased post RYGB but was suppressed after SADI-S. Leptin decreased markedly, and in an exploratory analysis, its decrease was associated with weight-loss success at 3 years. Weight loss was greater with SADI-S at 1 year, but not significantly different at 3 and 5 years; in an exploratory analysis, the increase in conjugated BAs correlated negatively with recurrence weight gain from nadir at 5 years. The SeHCAT test showed no bile acid malabsorption in SADI-S and normal retention in 90.6% of RYGB patients. Despite routine supplementation, total protein, zinc, copper, and the vitamin A/RBP and vitamin E/cholesterol ratios decreased after both techniques. Conclusions: In conclusion, RYGB and SADI-S are associated with differentiated BA and hormonal profiles. The predominance of conjugated BAs after SADI-S, which we hypothesize may be related to its longer biliopancreatic limb, emerges as a potential candidate mechanism for weight maintenance that requires confirmation and was not accompanied by clinically relevant bile acid malabsorption; however, the decreases observed in several micronutrients support careful nutritional follow-up after both techniques. Clinical trial registration: ISRCTN81954082.
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BibTeX
@article{jimenezvaras2026changes,
title = {{Changes in Bile Acid Metabolism and Nutrient-Stimulated Hormone Responses After Malabsorptive Metabolic Surgery: RYGB Versus SADI-S}},
author = {Inés Jiménez-Varas and Isabel Ortega-Madueño and Angélica Larrad-Sainz and Ana Barabash-Bustelo and Andrés Sánchez-Pernaute and Pilar Matía-Martín and Natalia Pérez-Ferre and Ana María Ramos-Leví and Clara Marcuello Foncillas and Gemma Hernández-Núñez and María Victoria Sáez de Parayuelos and María Jesús Pérez-Castejón and Antonio Torres-García and Alfonso L. Calle-Pascual and Miguel A. Rubio-Herrera},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18203398},
url = {https://www.mdpi.com/2072-6643/18/20/3398},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Changes in Bile Acid Metabolism and Nutrient-Stimulated Hormone Responses After Malabsorptive Metabolic Surgery: RYGB Versus SADI-S
AU - Inés Jiménez-Varas
AU - Isabel Ortega-Madueño
AU - Angélica Larrad-Sainz
AU - Ana Barabash-Bustelo
AU - Andrés Sánchez-Pernaute
AU - Pilar Matía-Martín
AU - Natalia Pérez-Ferre
AU - Ana María Ramos-Leví
AU - Clara Marcuello Foncillas
AU - Gemma Hernández-Núñez
AU - María Victoria Sáez de Parayuelos
AU - María Jesús Pérez-Castejón
AU - Antonio Torres-García
AU - Alfonso L. Calle-Pascual
AU - Miguel A. Rubio-Herrera
PY - 2026
DA - 2026/10/16
JO - Nutrients
DO - 10.3390/nu18203398
UR - https://www.mdpi.com/2072-6643/18/20/3398
AB - Background/Objectives: Bariatric–metabolic surgery (BMS) improves obesity through neuroendocrine mechanisms involving bile acids (BAs) and nutrient-stimulated gastrointestinal hormones. However, the underlying pathophysiology involved remains poorly understood. BAs are essential for the digestion and absorption of dietary fat and fat-soluble vitamins and act as nutrient-responsive signaling molecules, so their handling after malabsorptive procedures is relevant both to metabolic outcomes and to nutritional status. Methods: We prospectively compared Roux-en-Y gastric bypass (RYGB) and single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) in a single-center case-control study including 37 RYGB and 31 SADI-S patients with severe obesity and 19 non-obese controls. Before and one year after surgery, participants underwent a standardized mixed-meal test (nutrient challenge) with measurement of 14 individual BA fractions, insulin, GLP-1, ghrelin, FGF19, leptin, and adiponectin; bile acid malabsorption was assessed one year after surgery with the 75Se-SeHCAT test, and weight was followed for up to 5 years. Results: Fasting total BAs increased after both techniques, with no significant between-technique difference in total BA exposure (primary outcome). The techniques were associated with distinct BA profiles: fasting concentrations of conjugated BAs (GCA, GCDCA, and TDCA) were higher after SADI-S than after RYGB (FDR-adjusted q < 0.05), with a similar but more variable pattern in postprandial AUCs, whereas RYGB was characterized by a greater postprandial rise in the unconjugated secondary BA DCA. After surgery, FGF19 increased progressively during the mixed-meal test, peaking at 90 min, and its increase correlated with the rise in conjugated BAs, particularly in SADI-S. The postprandial insulin peak shifted earlier in both techniques, with a lower insulin AUC in SADI-S; GLP-1 responses were supraphysiological, and ghrelin increased post RYGB but was suppressed after SADI-S. Leptin decreased markedly, and in an exploratory analysis, its decrease was associated with weight-loss success at 3 years. Weight loss was greater with SADI-S at 1 year, but not significantly different at 3 and 5 years; in an exploratory analysis, the increase in conjugated BAs correlated negatively with recurrence weight gain from nadir at 5 years. The SeHCAT test showed no bile acid malabsorption in SADI-S and normal retention in 90.6% of RYGB patients. Despite routine supplementation, total protein, zinc, copper, and the vitamin A/RBP and vitamin E/cholesterol ratios decreased after both techniques. Conclusions: In conclusion, RYGB and SADI-S are associated with differentiated BA and hormonal profiles. The predominance of conjugated BAs after SADI-S, which we hypothesize may be related to its longer biliopancreatic limb, emerges as a potential candidate mechanism for weight maintenance that requires confirmation and was not accompanied by clinically relevant bile acid malabsorption; however, the decreases observed in several micronutrients support careful nutritional follow-up after both techniques. Clinical trial registration: ISRCTN81954082.
SN - 2072-6643
ER -