Post-prandial serum bile acid concentration change after bariatric surgery and is associated with weight loss and glucose metabolism improvement in obese human subjects

Background and aim Experimental data suggest that surgically induced changes in bile acid (BA) and farnesoid X receptor (FXR) signalling could be involved in bariatric surgery induced body weight reduction and improvement of glucose metabolism, but no data are available in humans. Methods An oral lipid tolerance test (OLTT), with blood sampling at 0, 90 and 120 minutes, was performed at baseline and 6 months after sleeve gastrectomy (SG) in 43 obese subjects. BA serum concentration was measured by ultra-performance liquid chromatography-mass spectrometry and serum fibroblast growth factor 19 (FGF19) by ELISA. Data are reported as median values (interquartile range). Results Six months after SG, compared to baseline, there was a reduction of BMI [31.8 Kg/m2 (28.9-35.9) vs 42.4 Kg/m2 (38.4-50.8); p<0.001] and glycated haemoglobin (HbA1c) [5.0 (4.7-5.2) vs 5.3 (5.1-5.8); p<0.001]. When patients with a 6 month percent weight loss above the median value (HWL) were separately analysed from those below the median value (LWL), 6 months after SG, compared to baseline, the serum BA concentration area under the curve (AUC) during OLTT, was significantly higher in the HWL [299316 (151314-497162) vs 173644 (135325-259974); p<0.05] but not in the LWL group [238670 (182744-523977) vs 182876 (142030-223285); p=ns]. When patients with a 6 month better glucose metabolism improvement (percent reduction of HbA1c above the median value; BGMI) were separately analysed from those with a worse glucose metabolism improvement (percent reduction of HbA1c below the median value; WGMI), 6 months after SG, compared to baseline: 1) the serum BA concentration AUC during OLTT, was significantly higher in the BGMI [316884 (200118-50135) vs 165500 (137161-216806); p<0.05] but not in in the WGMI group [260987 (154398-611641) vs 219310 (111475-287174); p=ns]; 2) FGF19 serum concentration during OLTT, was significantly higher at T0 [0.16 (0.1-0.22) vs 0.1 (0.05-0.14); p<0.05] and T120 [0.18 (0.08-0.32) vs 0.12 (0.05-0.18) p<0.05] only in the BGMI group. Conclusions Six months after SG patients with higher post-prandial serum levels of circulating BA have the best results in body weight reduction and improvement of glucose metabolism. Such metabolic effect could be mediated by the interaction of BA with FXR, with the subsequent release of FGF19.