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Peer-reviewedCC BY 4.0Nutrients

Changes in Bile Acid Metabolism and Nutrient-Stimulated Hormone Responses After Malabsorptive Metabolic Surgery: RYGB Versus SADI-S

3 more authors
6 affiliations
  1. 1Department of Endocrinology and Nutrition, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
  2. 2Department of Clinical Analysis, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
  3. 3Department of General Surgery, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
  4. 4Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
  5. 5Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain
  6. 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  -