TY - JOUR

T1 - Enterohepatic, gluco-metabolic, and gut microbial characterization of individuals with bile acid malabsorption

AU - Kårhus, Martin Lund

AU - Sonne, David Peick

AU - Thomasen, Martin

AU - Ellegaard, Anne-Marie

AU - Holst, Jens Juul

AU - Rehfeld, Jens Frederik

AU - Chávez-Talavera, Oscar

AU - Tailleux, Anne

AU - Staels, Bart

AU - Nielsen, Dennis Sandris

AU - Dragsted, Lars Ove

AU - Vilsbøll, Tina

AU - Brønden, Andreas

AU - Knop, Filip Krag

N1 - CURIS 2022 NEXS 094

PY - 2022

Y1 - 2022

N2 - Background and aims: Bile acid malabsorption (BAM) is a debilitating disease characterized by loose stools and high stool frequency. The pathophysiology of BAM is not wellunderstood. We investigated postprandial enterohepatic and gluco-metabolic physiology, as well as gut microbiome composition and fecal bile acid content in patients with BAM.Methods: 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. Results: Patients with BAM were characterized by increased bile acid synthesisas 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 Blautia, Streptococcus, Ruminococcus gnavus,and Akkermansia muciniphila. Conclusion: 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.

AB - Background and aims: Bile acid malabsorption (BAM) is a debilitating disease characterized by loose stools and high stool frequency. The pathophysiology of BAM is not wellunderstood. We investigated postprandial enterohepatic and gluco-metabolic physiology, as well as gut microbiome composition and fecal bile acid content in patients with BAM.Methods: 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. Results: Patients with BAM were characterized by increased bile acid synthesisas 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 Blautia, Streptococcus, Ruminococcus gnavus,and Akkermansia muciniphila. Conclusion: 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.

KW - Faculty of Science

KW - Glucose metabolism

KW - Gut microbiota

KW - Pathophysiology

KW - Prediabetic

U2 - 10.1016/j.gastha.2021.12.007

DO - 10.1016/j.gastha.2021.12.007

M3 - Journal article

VL - 1

SP - 299

EP - 312

JO - Gastro Hep Advances

JF - Gastro Hep Advances

SN - 2772-5723

IS - 3

ER -