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Gastro hep advances · 2022

Enterohepatic, Gluco-metabolic, and Gut Microbial Characterization of Individuals With Bile Acid Malabsorption.

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Kårhus Martin L, Sonne David P, Thomasen Martin, Ellegaard Anne-Marie, Holst Jens J, Rehfeld Jens F, Chávez-Talavera Oscar, Tailleux Anne, Staels Bart, Nielsen Dennis S, Krych Lukasz, Dragsted Lars O, Vilsbøll Tina, Brønden Andreas, Knop Filip K

Аннотация

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 well-understood. 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.

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

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