Sorbonne Universités, UPMC, INSERM ERL1157, CNRS UMR 7203 LBM, CHU Saint Antoine, Paris, France.
Sorbonne Universités, UPMC, INSERM ERL1157, CNRS UMR 7203 LBM, CHU Saint Antoine, Paris, France
J Lipid Res. 2018 Nov;59(11):2202-2213. doi: 10.1194/jlr.M084830. Epub 2018 Sep 11.
Bile acid (BA) secretion and circulation in chronic pancreatitis (CP) patients with exocrine pancreatic insufficiency (EPI) were investigated by simultaneously measuring postprandial levels of individual BAs in duodenal contents and blood plasma using LC-MS/MS. CP patients and healthy volunteers (HVs) were intubated with gastric and duodenal tubes prior to the administration of a test meal and continuous aspiration of duodenal contents. Pancreatic lipase outputs in CP patients were very low (0.7 ± 0.2 mg) versus HVs (116.7 ± 68.1 mg; < 0.005), thus confirming the severity of EPI. Duodenal BA outputs were reduced in CP patients (1.00 ± 0.89 mmol; 0.47 ± 0.42 g) versus HVs (5.52 ± 4.53 mmol; 2.62 ± 2.14 g; < 0.15). Primary to secondary BA ratio was considerably higher in CP patients (38.09 ± 48.1) than HVs (4.15 ± 2.37; < 0.15), indicating an impaired transformation of BAs by gut microbiota. BA concentrations were found below the critical micellar concentration in CP patients, while a high BA concentration peak corresponding to gallbladder emptying was evidenced in HVs. Conversely, BA plasma concentration was increased in CP patients versus HVs suggesting a cholangiohepatic shunt of BA secretion. Alterations of BA circulation and levels may result from the main biliary duct stenosis observed in these CP patients and may aggravate the consequences of EPI on lipid malabsorption.
采用 LC-MS/MS 同时测量餐后十二指肠内容物和血浆中个体胆汁酸(BA)的水平,研究慢性胰腺炎(CP)伴胰外分泌功能不全(EPI)患者的胆汁酸分泌和循环。CP 患者和健康志愿者(HV)在给予试验餐和连续抽吸十二指肠内容物之前,通过胃管和十二指肠管进行插管。CP 患者的胰腺脂肪酶产量非常低(0.7 ± 0.2 mg),而 HV 为(116.7 ± 68.1 mg;<0.005),证实了 EPI 的严重程度。CP 患者的十二指肠 BA 产量降低(1.00 ± 0.89 mmol;0.47 ± 0.42 g),而 HV 为(5.52 ± 4.53 mmol;2.62 ± 2.14 g;<0.15)。CP 患者的初级到次级 BA 比值明显高于 HV(38.09 ± 48.1)比 HV(4.15 ± 2.37;<0.15),表明肠道微生物群对 BA 的转化受损。CP 患者的 BA 浓度低于胶束临界浓度,而 HV 则出现与胆囊排空相对应的高 BA 浓度峰。相反,CP 患者的 BA 血浆浓度高于 HV,表明 BA 分泌的胆肝分流增加。BA 循环和水平的改变可能是由于这些 CP 患者主要胆管狭窄引起的,可能会加重 EPI 对脂质吸收不良的影响。