Enterohepatic, gluco-metabolic, and gut microbial characterization of individuals with bile acid malabsorption
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Enterohepatic, gluco-metabolic, and gut microbial characterization of individuals with bile acid malabsorption. / Kårhus, Martin Lund; Sonne, David Peick; Thomasen, Martin ; Ellegaard, Anne-Marie; Holst, Jens Juul; Rehfeld, Jens Frederik; Chávez-Talavera, Oscar; Tailleux, Anne; Staels, Bart; Nielsen, Dennis Sandris; Dragsted, Lars Ove; Vilsbøll, Tina; Brønden, Andreas; Knop, Filip Krag.
I: Gastro Hep Advances, Bind 1, Nr. 3, 2022, s. 299-312.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 301720014