Document Detail


Modulation of the fecal bile acid profile by gut microbiota in cirrhosis.
MedLine Citation:
PMID:  23333527     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: The 7α-dehydroxylation of primary bile acids (BAs), chenodeoxycholic (CDCA) and cholic acid (CA) into the secondary BAs, lithocholic (LCA) and deoxycholic acid (DCA), is a key function of the gut microbiota. We aimed at studying the linkage between fecal BAs and gut microbiota in cirrhosis since this could help understand cirrhosis progression.
METHODS: Fecal microbiota were analyzed by culture-independent multitagged-pyrosequencing, fecal BAs using HPLC and serum BAs using LC-MS in controls, early (Child A) and advanced cirrhotics (Child B/C). A subgroup of early cirrhotics underwent BA and microbiota analysis before/after eight weeks of rifaximin.
RESULTS: Cross-sectional: 47 cirrhotics (24 advanced) and 14 controls were included. In feces, advanced cirrhotics had the lowest total, secondary, secondary/primary BA ratios, and the highest primary BAs compared to early cirrhotics and controls. Secondary fecal BAs were detectable in all controls but in a significantly lower proportion of cirrhotics (p<0.002). Serum primary BAs were higher in advanced cirrhotics compared to the rest. Cirrhotics, compared to controls, had a higher Enterobacteriaceae (potentially pathogenic) but lower Lachonospiraceae, Ruminococcaceae and Blautia (7α-dehydroxylating bacteria) abundance. CDCA was positively correlated with Enterobacteriaceae (r=0.57, p<0.008) while Ruminococcaceae were positively correlated with DCA (r=0.4, p<0.05). A positive correlation between Ruminococcaceae and DCA/CA (r=0.82, p<0.012) and Blautia with LCA/CDCA (r=0.61, p<0.03) was also seen. Prospective study: post-rifaximin, six early cirrhotics had reduction in Veillonellaceae and in secondary/primary BA ratios.
CONCLUSIONS: Cirrhosis, especially advanced disease, is associated with a decreased conversion of primary to secondary fecal BAs, which is linked to abundance of key gut microbiome taxa.
Authors:
Genta Kakiyama; William M Pandak; Patrick M Gillevet; Phillip B Hylemon; Douglas M Heuman; Kalyani Daita; Hajime Takei; Akina Muto; Hiroshi Nittono; Jason M Ridlon; Melanie B White; Nicole A Noble; Pamela Monteith; Michael Fuchs; Leroy R Thacker; Masoumeh Sikaroodi; Jasmohan S Bajaj
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-01-16
Journal Detail:
Title:  Journal of hepatology     Volume:  58     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2014-02-11     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  949-55     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Anti-Infective Agents / therapeutic use
Bile Acids and Salts / analysis*
Case-Control Studies
Cross-Sectional Studies
Enterobacteriaceae / isolation & purification,  physiology
Feces / chemistry*
Female
Humans
Intestines / microbiology*
Liver Cirrhosis / metabolism*
Male
Microbiota / physiology*
Middle Aged
Prospective Studies
Rifamycins / therapeutic use
Ruminococcus / isolation & purification,  physiology
Veillonellaceae / isolation & purification,  physiology
Grant Support
ID/Acronym/Agency:
R01 AA020203/AA/NIAAA NIH HHS; R01 DK087913/DK/NIDDK NIH HHS; R01AA020203/AA/NIAAA NIH HHS; R01DK087913/DK/NIDDK NIH HHS; U01 AT004428/AT/NCCAM NIH HHS; U01AT004428/AT/NCCAM NIH HHS; UL1 TR000058/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Infective Agents; 0/Bile Acids and Salts; 0/Rifamycins; 88747-56-2/rifaximin

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