Liraglutide and Colesevelam Change Serum and Fecal Bile Acid Levels in a Randomized Trial With Patients With Bile Acid Diarrhea.

IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Anne-Marie Ellegaard, Martin L Kårhus, Lukasz Krych, David P Sonne, Julie L Forman, Svend H Hansen, Lars Ove Dragsted, Dennis S Nielsen, Filip K Knop
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引用次数: 0

Abstract

Introduction: Both liraglutide and colesevelam improve bile acid diarrhea symptoms. Colesevelam binds excess amounts of diarrhea-causing bile acids in the colon, whereas the mode of action for liraglutide remains elusive. In this article, we examined the impact of colesevelam and liraglutide treatment on the concentrations of bile acids in serum and feces and the fecal microbiota composition to better understand the 2 drugs' modes of action.

Methods: Bile acid species were analyzed in serum and fecal samples from a randomized, double-blind, double-dummy trial at baseline and after 3 and 6 weeks of orally administered colesevelam (1,875 mg twice daily, n = 26) or subcutaneously administered liraglutide (uptitrated by weekly increments of 0.6 mg from 0.6 to 1.8 mg daily, n = 26) in patients with 75 selenium-homotaurocholic acid test-verified, idiopathic, or postcholecystectomy bile acid diarrhea. Fecal microbiota composition was analyzed by 16S rRNA gene amplicon sequencing at the same time points.

Results: Colesevelam increased the fecal concentrations of all bile acid species, whereas it decreased serum concentrations of secondary bile acids. Liraglutide induced a small increase in serum unconjugated bile acid concentrations without affecting fecal bile acid concentrations. No changes in fecal microbiota composition were observed with either treatment.

Discussion: Colesevelam and liraglutide exhibit distinct effects on serum and fecal bile acid concentrations with colesevelam reducing serum concentrations of secondary bile acids and promoting fecal bile acid excretion, whereas liraglutide enhances serum concentrations of unconjugated bile acids, potentially through deceleration of small intestinal transit time allowing more time for passive absorption of bile acids.

在一项针对胆汁酸腹泻患者的随机试验中,利拉鲁肽和可乐定会改变血清和粪便中的胆汁酸水平。
简介利拉鲁肽和可乐塞维兰都能改善胆汁酸腹泻症状。可乐塞维兰能结合结肠中过量的导致腹泻的胆汁酸,而利拉鲁肽的作用模式仍不明确。本文研究了可乐塞韦仑和利拉鲁肽治疗对血清和粪便中胆汁酸浓度以及粪便微生物群组成的影响,以更好地了解这两种药物的作用模式:在口服可乐塞韦兰(1,875 毫克,每天两次,n = 26)或皮下注射利拉鲁肽(每周递增 0.6 毫克,每天 0.6 至 1.8 毫克,n = 26)。在相同的时间点,通过 16S rRNA 基因扩增片测序分析了粪便微生物群的组成:结果:可乐西维兰增加了粪便中所有胆汁酸种类的浓度,而降低了血清中次级胆汁酸的浓度。利拉鲁肽会使血清中的非结合胆汁酸浓度略有增加,但不会影响粪便中的胆汁酸浓度。两种治疗方法均未观察到粪便微生物群组成的变化:讨论:可乐塞韦兰和利拉鲁肽对血清和粪便中胆汁酸的浓度有不同的影响,可乐塞韦兰可降低血清中次级胆汁酸的浓度,促进粪便中胆汁酸的排泄,而利拉鲁肽可提高血清中非结合胆汁酸的浓度,这可能是通过减慢小肠的转运时间,使胆汁酸有更多的时间被动吸收。
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来源期刊
Clinical and Translational Gastroenterology
Clinical and Translational Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
7.00
自引率
0.00%
发文量
114
审稿时长
16 weeks
期刊介绍: Clinical and Translational Gastroenterology (CTG), published on behalf of the American College of Gastroenterology (ACG), is a peer-reviewed open access online journal dedicated to innovative clinical work in the field of gastroenterology and hepatology. CTG hopes to fulfill an unmet need for clinicians and scientists by welcoming novel cohort studies, early-phase clinical trials, qualitative and quantitative epidemiologic research, hypothesis-generating research, studies of novel mechanisms and methodologies including public health interventions, and integration of approaches across organs and disciplines. CTG also welcomes hypothesis-generating small studies, methods papers, and translational research with clear applications to human physiology or disease. Colon and small bowel Endoscopy and novel diagnostics Esophagus Functional GI disorders Immunology of the GI tract Microbiology of the GI tract Inflammatory bowel disease Pancreas and biliary tract Liver Pathology Pediatrics Preventative medicine Nutrition/obesity Stomach.
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