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

Martin Lund Kårhus, David Peick Sonne, Martin Thomasen, Anne-Marie Ellegaard, Jens Juul Holst, Jens Frederik Rehfeld, Oscar Chávez-Talavera, Anne Tailleux, Bart Staels, Dennis Sandris Nielsen, Lars Ove Dragsted, Tina Vilsbøll, Andreas Brønden, Filip Krag Knop*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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 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 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.
Original languageEnglish
JournalGastro Hep Advances
Volume1
Issue number3
Pages (from-to)299-312
Number of pages14
ISSN2772-5723
DOIs
Publication statusPublished - 2022

Keywords

  • Faculty of Science
  • Glucose metabolism
  • Gut microbiota
  • Pathophysiology
  • Prediabetic

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