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.