Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy.
Amidohydrolases
/ genetics
Animals
Bacteroidetes
/ drug effects
Case-Control Studies
Cholestasis, Intrahepatic
/ microbiology
Female
Gastrointestinal Microbiome
/ drug effects
Gene Expression Regulation, Bacterial
Humans
Intestines
/ microbiology
Mice
Pregnancy
Pregnancy Complications
/ microbiology
Ursodeoxycholic Acid
/ pharmacology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 03 2020
03 03 2020
Historique:
received:
24
10
2019
accepted:
10
01
2020
entrez:
5
3
2020
pubmed:
5
3
2020
medline:
25
11
2020
Statut:
epublish
Résumé
Ursodeoxycholic acid (UDCA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut environment in ICP to alter enterohepatic signalling. The gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDCA (Fisher's exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDCA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. These demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19.
Identifiants
pubmed: 32127609
doi: 10.1038/s41598-020-60821-w
pii: 10.1038/s41598-020-60821-w
pmc: PMC7054423
doi:
Substances chimiques
Ursodeoxycholic Acid
724L30Y2QR
Amidohydrolases
EC 3.5.-
choloylglycine hydrolase
EC 3.5.1.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3895Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P028225/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R000875/1
Pays : United Kingdom
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