Kårhus Martin L, Sonne David P, Thomasen Martin, Ellegaard Anne-Marie, Holst Jens J, Rehfeld Jens F, Chávez-Talavera Oscar, Tailleux Anne, Staels Bart, Nielsen Dennis S, Krych Lukasz, Dragsted Lars O, Vilsbøll Tina, Brønden Andreas, Knop Filip K
Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Gastro Hep Adv. 2022 Mar 30;1(3):299-312. doi: 10.1016/j.gastha.2021.12.007. eCollection 2022.
Bile acid malabsorption (BAM) is a debilitating disease characterized by loose stools and high stool frequency. The pathophysiology of BAM is not well-understood. We investigated postprandial enterohepatic and gluco-metabolic physiology, as well as gut microbiome composition and fecal bile acid content in patients with BAM.
Twelve participants with selenium-75 homocholic acid taurine test-verified BAM and 12 healthy controls, individually matched on sex, age, and body mass index, were included. Each participant underwent 2 mixed meal tests (with and without administration of the bile acid sequestrant colesevelam) with blood sampling and evaluation of gallbladder motility; bile acid content and microbiota composition were evaluated in fecal specimens.
Patients with BAM were characterized by increased bile acid synthesis as assessed by circulating 7-alpha-hydroxy-4-cholesten-3-one, fecal bile acid content, and postprandial concentrations of glucose, insulin, C-peptide, and glucagon. The McAuley index of insulin sensitivity was lower in patients with BAM than that in healthy controls. In patients with BAM, colesevelam co-administered with the meal reduced postprandial concentrations of bile acids and fibroblast growth factor 19 and increased 7-alpha-hydroxy-4-cholesten-3-one concentrations but did not affect postprandial glucagon-like peptide 1 responses or other gluco-metabolic parameters. Patients with BAM were characterized by a gut microbiome with low relative abundance of bifidobacteria and high relative abundance of , , , and .
Patients with BAM are characterized by an overproduction of bile acids, greater fecal bile acid content, and a gluco-metabolic profile indicative of a dysmetabolic prediabetic-like state, with changes in their gut microbiome composition potentially linking their enterohepatic pathophysiology and their dysmetabolic phenotype. ClinicalTrials.gov number NCT03009916.
胆汁酸吸收不良（BAM）是一种以腹泻和高排便频率为特征的使人衰弱的疾病。BAM的病理生理学尚未完全了解。我们研究了BAM患者的餐后肠肝循环和糖代谢生理学，以及肠道微生物群组成和粪便胆汁酸含量。
纳入12名经硒-75高牛磺胆酸试验验证的BAM患者和12名健康对照者，根据性别、年龄和体重指数进行个体匹配。每位参与者进行2次混合餐试验（一次服用胆汁酸螯合剂考来维仑，一次不服用），同时进行血液采样和胆囊运动评估；对粪便样本中的胆汁酸含量和微生物群组成进行评估。
通过循环中的7-α-羟基-4-胆甾烯-3-酮、粪便胆汁酸含量以及餐后葡萄糖、胰岛素、C肽和胰高血糖素浓度评估，BAM患者的胆汁酸合成增加。BAM患者的麦考利胰岛素敏感性指数低于健康对照者。在BAM患者中，与餐同服考来维仑可降低餐后胆汁酸和成纤维细胞生长因子19的浓度，并增加7-α-羟基-4-胆甾烯-3-酮的浓度，但不影响餐后胰高血糖素样肽1反应或其他糖代谢参数。BAM患者的肠道微生物群特征为双歧杆菌相对丰度低，而[此处原文缺失几种菌名]、[此处原文缺失几种菌名]、[此处原文缺失几种菌名]和[此处原文缺失几种菌名]相对丰度高。
BAM患者的特征是胆汁酸过度生成、粪便胆汁酸含量增加以及糖代谢特征表明存在代谢紊乱的糖尿病前期样状态，其肠道微生物群组成的变化可能将其肠肝病理生理学与代谢紊乱表型联系起来。ClinicalTrials.gov编号：NCT03009916。
